{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T17:27:10Z","timestamp":1767374830864,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T00:00:00Z","timestamp":1711584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: DICER1, a cancer predisposition syndrome (CPS), seems to escape timely diagnosis in pediatric patients. Case report 1: A 16-year-old female patient was referred to the endocrinology ward due to a large goiter. Her medical history indicated normal sexual maturation, with menarche occurring at 13.5 years. Over the past 2.5 years, she had developed pronounced androgenic symptoms, including a deepened male voice; facial, back, and neckline acne; hirsutism; and menstrual irregularities leading to secondary amenorrhea. A thyroid ultrasound identified a multinodular goiter (MNG) with cystic\u2013solid lesions containing calcifications. An abdominal ultrasound identified a 5.7 \u00d7 6.9 cm solid mass in the right adnexal region, displacing the uterus to the left. Histopathological examination confirmed a Sertoli\u2013Leydig cell tumor. The patient was subjected to a total thyroidectomy. Histopathology revealed benign follicular cell-derived neoplasms. Thyroid follicular nodular disease (TFND) was diagnosed bilaterally. DNA analysis using NGS, confirmed via the Sanger method, revealed a pathogenic heterozygotic variant c.2953C&gt;T [p.Gln985*] in exon 18 of the DICER1 gene. Case report 2: A 12-year-old male patient was admitted to the pediatric surgery unit due to a 33 mL goiter. A month prior to his admission, the patient discovered a palpable nodule in his neck, accompanied by hoarseness. An ultrasound revealed MNG. Molecular analysis revealed a pathogenic heterozygotic variant c.2782C&gt;T [p.Gln928*] in exon 17 of the DICER1 gene. Subsequently, a total thyroidectomy was performed, and histopathological examination revealed TFND bilaterally. Conclusions: Recent advances in genetic evaluation and in histological approaches indicate that MNG\/TFND, although rare in the pediatric population, when accompanied by characteristic ultrasound and histopathological features, and by additional features such as androgenization, may warrant assessment also of the DICER1 gene within CPS molecular panel screening.<\/jats:p>","DOI":"10.3390\/children11040403","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T12:52:12Z","timestamp":1711630332000},"page":"403","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Ultrasound\u2013Histopathological Presentation of Thyroid and Ovary Lesions in Adolescent Patients with DICER1 Syndrome: Case Reports and Literature Overview"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3870-368X","authenticated-orcid":false,"given":"Dominika","family":"Janu\u015b","sequence":"first","affiliation":[{"name":"Department of Pediatric and Adolescent Endocrinology, Jagiellonian University Medical College, 31-008 Krakow, Poland"},{"name":"Department of Pediatric and Adolescent Endocrinology, University Children\u2019s Hospital in Krakow, 30-663 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8191-4239","authenticated-orcid":false,"given":"Monika","family":"Kujdowicz","sequence":"additional","affiliation":[{"name":"Department of Pathomorphology, Jagiellonian University Medical College, 31-008 Krakow, Poland"},{"name":"Department of Pathology, University Children\u2019s Hospital in Krakow, 30-663 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konrad","family":"Kaleta","sequence":"additional","affiliation":[{"name":"Student Scientific Group of Pediatric Endocrinology, Department of Pediatric and Adolescent Endocrinology, Jagiellonian University Medical College, 31-008 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamil","family":"Mo\u017cd\u017ce\u0144","sequence":"additional","affiliation":[{"name":"Student Scientific Group of Pediatric Endocrinology, Department of Pediatric and Adolescent Endocrinology, Jagiellonian University Medical College, 31-008 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Radli\u0144ski","sequence":"additional","affiliation":[{"name":"Student Scientific Group of Pediatric Endocrinology, Department of Pediatric and Adolescent Endocrinology, Jagiellonian University Medical College, 31-008 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Taczanowska-Niemczuk","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Jagiellonian University Medical College, 31-008 Krakow, Poland"},{"name":"Department of Pediatric Surgery, University Children\u2019s Hospital in Krakow, 30-663 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Kiszka-Wi\u0142koj\u0107","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Jagiellonian University Medical College, 31-008 Krakow, Poland"},{"name":"Department of Pediatric Surgery, University Children\u2019s Hospital in Krakow, 30-663 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcin","family":"Ma\u015blanka","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Jagiellonian University Medical College, 31-008 Krakow, Poland"},{"name":"Department of Pediatric Surgery, University Children\u2019s Hospital in Krakow, 30-663 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wojciech","family":"G\u00f3recki","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Jagiellonian University Medical College, 31-008 Krakow, Poland"},{"name":"Department of Pediatric Surgery, University Children\u2019s Hospital in Krakow, 30-663 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerzy B.","family":"Starzyk","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adolescent Endocrinology, Jagiellonian University Medical College, 31-008 Krakow, Poland"},{"name":"Department of Pediatric and Adolescent Endocrinology, University Children\u2019s Hospital in Krakow, 30-663 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41379-021-00905-8","article-title":"DICER1 tumor predisposition syndrome: An evolving story initiated with the pleuropulmonary blastoma","volume":"35","author":"Stewart","year":"2022","journal-title":"Mod. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/35053110","article-title":"Role for a bidentate ribonuclease in the initiation step of RNA interference","volume":"409","author":"Bernstein","year":"2001","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.neo.2015.08.003","article-title":"The oncogenic roles of DICER1 RNase IIIb domain mutations in ovarian Sertoli-Leydig cell tumors","volume":"17","author":"Wang","year":"2015","journal-title":"Neoplasia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1136\/jmg.2010.083790","article-title":"DICER1 syndrome: Clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome","volume":"48","author":"Slade","year":"2011","journal-title":"J. Med. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1055\/s-0033-1337976","article-title":"DICER1 syndrome: A new cancer syndrome","volume":"225","author":"Graf","year":"2013","journal-title":"Klin. Padiatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s00401-014-1318-7","article-title":"Germ-line and somatic DICER1 mutations in pineoblastoma","volume":"128","author":"Sabbaghian","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s00401-014-1285-z","article-title":"Pituitary blastoma: A pathognomonic feature of germ-line DICER1 mutations","volume":"128","author":"Sabbaghian","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Robertson, J.C., Jorcyk, C.L., and Oxford, J.T. (2018). DICER1 Syndrome: DICER1 Mutations in Rare Cancers. Cancers, 10.","DOI":"10.3390\/cancers10050143"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1200\/JCO.2018.78.4678","article-title":"Neoplasm Risk Among Individuals With a Pathogenic Germline Variant in DICER1","volume":"37","author":"Stewart","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"614541","DOI":"10.3389\/fonc.2020.614541","article-title":"DICER1 Syndrome and Cancer Predisposition: From a Rare Pediatric Tumor to Lifetime Risk","volume":"10","author":"Caroleo","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Riascos, M.C., Huynh, A., Faquin, W.C., and Nos\u00e9, V. (2024). Expanding Our Knowledge of DICER1 Gene Alterations and Their Role in Thyroid Diseases. Cancers, 16.","DOI":"10.3390\/cancers16020347"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5295","DOI":"10.1038\/onc.2014.150","article-title":"Exome sequencing of pleuropulmonary blastoma reveals frequent biallelic loss of TP53 and two hits in DICER1 resulting in retention of 5p-derived miRNA hairpin loop sequences","volume":"33","author":"Pugh","year":"2014","journal-title":"Oncogene"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e210112","DOI":"10.1001\/jamanetworkopen.2021.0112","article-title":"A Genome-First Approach to Characterize DICER1 Pathogenic Variant Prevalence, Penetrance, and Phenotype","volume":"4","author":"Mirshahi","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1002\/ijc.30907","article-title":"The prevalence of DICER1 pathogenic variation in population databases","volume":"141","author":"Kim","year":"2017","journal-title":"Int. J. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1038\/gim.2016.83","article-title":"Macrocephaly associated with the DICER1 syndrome","volume":"19","author":"Khan","year":"2017","journal-title":"Genet. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"128","DOI":"10.3174\/ajnr.A8039","article-title":"Newly Recognized Genetic Tumor Syndromes of the CNS in the 5th WHO Classification: Imaging Overview with Genetic Updates","volume":"45","author":"Agarwal","year":"2024","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1111\/cen.14074","article-title":"Multinodular goitre is a gateway for molecular testing of DICER1 syndrome","volume":"91","author":"Bertozzi","year":"2019","journal-title":"Clin. Endocrinol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1007\/s12105-022-01417-w","article-title":"Proceedings of the North American Society of Head and Neck Pathology, Los Angeles, CA, March 20, 2022: DICER1-Related Thyroid Tumors","volume":"16","author":"Sauer","year":"2022","journal-title":"Head Neck Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"703","DOI":"10.3803\/EnM.2022.1553","article-title":"Update from the 2022 World Health Organization Classification of Thyroid Tumors: A Standardized Diagnostic Approach","volume":"37","author":"Jung","year":"2022","journal-title":"Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1210\/jc.2016-2954","article-title":"Quantification of thyroid cancer and multinodular goiter risk in the DICER1 syndrome: A family-based cohort study","volume":"102","author":"Khan","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"E1072","DOI":"10.1210\/jc.2013-4206","article-title":"Exploring the association Between DICER1 mutations and differentiated thyroid carcinoma","volume":"99","author":"Sabbaghian","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e29017","DOI":"10.1002\/pbc.29017","article-title":"Consensus recommendations from the EXPeRT\/PARTNER groups for the diagnosis and therapy of sex cord stromal tumors in children and adolescents","volume":"68","author":"Schneider","year":"2021","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1158\/1078-0432.CCR-17-3089","article-title":"DICER1 and associated conditions: Identification of at-risk individuals and recommended surveillance strategies","volume":"24","author":"Schultz","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"173","DOI":"10.5603\/EP.a2022.0028","article-title":"Diagnosis and treatment of thyroid cancer in adult patients\u2014Recommendations of polish scientific societies and the national oncological strategy. 2022 update","volume":"73","author":"Dedecjus","year":"2022","journal-title":"Endokrynol. Polska"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1159\/000478927","article-title":"European Thyroid association guidelines for ultrasound malignancy risk stratification of thyroid nodules in adults: The EU-TIRADS","volume":"6","author":"Russ","year":"2017","journal-title":"Eur. Thyroid. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1089\/thy.2009.0274","article-title":"The Bethesda system for reporting thyroid cytopathology","volume":"19","author":"Cibas","year":"2009","journal-title":"Thyroid"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"15888","DOI":"10.1038\/s41598-022-19709-0","article-title":"Ultrasound features of multinodular goiter in DICER1 syndrome","volume":"12","author":"Niedziela","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"628","DOI":"10.5603\/EP.2016.0072","article-title":"Diagnostics and treatment of differentiated thyroid carcinoma in children\u2014Guidelines of polish national societies","volume":"67","author":"Niedziela","year":"2016","journal-title":"Endokrynol. Polska"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1089\/thy.2014.0460","article-title":"American Thyroid Association Guidelines Task Force. Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer","volume":"25","author":"Francis","year":"2015","journal-title":"Thyroid"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1170971","DOI":"10.3389\/fendo.2023.1170971","article-title":"Ultrasound, laboratory and histopathological insights in diagnosing papillary thyroid carcinoma in a paediatric population: A single centre follow-up study between 2000\u20132022","volume":"14","author":"Kujdowicz","year":"2023","journal-title":"Front. Endocrinol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.beem.2013.08.007","article-title":"Thyroid nodules","volume":"28","author":"Niedziela","year":"2014","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1210\/jc.2017-02698","article-title":"DICER1 Mutations Are Frequent in Adolescent-Onset Papillary Thyroid Carcinoma","volume":"103","author":"Wasserman","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s12022-020-09661-y","article-title":"Inherited Follicular Epithelial-Derived Thyroid Carcinomas: From Molecular Biology to Histological Correlates","volume":"32","author":"Mete","year":"2021","journal-title":"Endocr. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1111\/his.14416","article-title":"Macrofollicular variant follicular thyroid tumors are DICER1 mutated and exhibit distinct histological features","volume":"79","author":"Juhlin","year":"2021","journal-title":"Histopathology"},{"key":"ref_36","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":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1210\/jc.2015-2169","article-title":"DICER1 Mutations and Differentiated Thyroid Carcinoma: Evidence of a Direct Association","volume":"101","author":"Rutter","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1097\/PAS.0000000000002149","article-title":"Pediatric Sertoli-Leydig Cell Tumors of the Ovary: An Integrated Study of Clinicopathological Features, Pan-cancer-Targeted Next-generation Sequencing and Chromosomal Microarray Analysis From a Single Institution","volume":"48","author":"Yang","year":"2024","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.ygyno.2012.07.114","article-title":"A clinicopathological analysis of 40 cases of ovarian Sertoli-Leydig cell tumors","volume":"127","author":"Gui","year":"2012","journal-title":"Gynecol. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.tem.2004.11.004","article-title":"Signaling at the crossroads of gonad development","volume":"16","author":"Ross","year":"2005","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s10577-012-9274-3","article-title":"Mammalian sex determination-insights from humans and mice","volume":"20","author":"Eggers","year":"2012","journal-title":"Chromosom. Res."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/11\/4\/403\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:20:06Z","timestamp":1760106006000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/11\/4\/403"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,28]]},"references-count":41,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["children11040403"],"URL":"https:\/\/doi.org\/10.3390\/children11040403","relation":{},"ISSN":["2227-9067"],"issn-type":[{"type":"electronic","value":"2227-9067"}],"subject":[],"published":{"date-parts":[[2024,3,28]]}}}