DICER1-Related Pediatric Thyroid Neoplasm with Follicular and Morular Growth: A Tumor that Did Not Read the Textbook

de Kock L, Gill AJ, Mete O, Foulkes WD, Nosé V. DICER1 syndrome. In: WHO Classification of Tumours Editorial Board. Endocrine and neuroendocrine tumours. Lyon (France): International Agency for Research on Cancer; 2025. (WHO classification of tumours series, 5th ed.; vol. 10). https://publications.iarc.who.int/645.

Anglesio MS, Wang Y, Yang W, Senz J, Wan A, Heravi-Moussavi A, Salamanca C, Maines-Bandiera S, Huntsman DG, Morin GB. Cancer-associated somatic DICER1 hotspot mutations cause defective miRNA processing and reverse-strand expression bias to predominantly mature 3p strands through loss of 5p strand cleavage. J Pathol. 2013;229(3):400-9. https://doi.org/10.1002/path.4135. PMID: 23132766.

Ricarte-Filho JC, Casado-Medrano V, Reichenberger E, Spangler Z, Scheerer M, Isaza A, Baran J, Patel T, MacFarland SP, Brodeur GM, Stewart DR, Baloch Z, Bauer AJ, Wasserman JD, Franco AT. DICER1 RNase IIIb domain mutations trigger widespread miRNA dysregulation and MAPK activation in pediatric thyroid cancer. Front Endocrinol (Lausanne). 2023;14:1083382. https://doi.org/10.3389/fendo.2023.1083382. PMID: 36896180; PMCID: PMC9990750.

Capozzi A, Jansen FA, Smetsers SE, Bakhuizen JJ, Hiemcke-Jiwa LS, Kranendonk MEG, Flucke U, Alaggio R, de Krijger RR. The Histological Spectrum of DICER1-Associated Neoplasms. Pediatr Dev Pathol. 2025:10935266251329752. https://doi.org/10.1177/10935266251329752. PMID: 40231379.

Cameselle-Teijeiro JM, Erickson LA, LiVolsi V, Nosé V. Syndromic familial follicular cell-derived thyroid tumours. In: WHO Classification of Tumours Editorial Board. Endocrine and neuroendocrine tumours. Lyon (France): International Agency for Research on Cancer; 2025. (WHO classification of tumours series, 5th ed.; vol. 10). https://publications.iarc.who.int/645.

Chernock RD, Rivera B, Borrelli N, Hill DA, Fahiminiya S, Shah T, Chong AS, Aqil B, Mehrad M, Giordano TJ, Sheridan R, Rutter MM, Dehner LP, Foulkes WD, Nikiforov YE. Poorly differentiated thyroid carcinoma of childhood and adolescence: a distinct entity characterized by DICER1 mutations. Mod Pathol. 2020;33(7):1264-1274. https://doi.org/10.1038/s41379-020-0458-7. PMID: 31937902; PMCID: PMC7329587.

Yegen G, Altay AY, Yılmaz İ, İşcan Y, Sormaz İC, Aksakal N, Önder S, Mete Ö. DICER1 Mutations Do Not Always Indicate Dismal Prognosis in Pediatric Poorly Differentiated Thyroid Carcinomas. Endocr Pathol. 2023;34(3):279-286. https://doi.org/10.1007/s12022-023-09780-2. PMID: 37574466.

Agaimy A, Witkowski L, Stoehr R, Cuenca JCC, González-Muller CA, Brütting A, Bährle M, Mantsopoulos K, Amin RMS, Hartmann A, Metzler M, Amr SS, Foulkes WD, Sobrinho-Simões M, Eloy C. Malignant teratoid tumor of the thyroid gland: an aggressive primitive multiphenotypic malignancy showing organotypical elements and frequent DICER1 alterations-is the term "thyroblastoma" more appropriate? Virchows Arch. 2020;477(6):787-798. https://doi.org/10.1007/s00428-020-02853-1. PMID: 32507920; PMCID: PMC7683491.

Cameselle-Teijeiro JM, Mete O, Asa SL, LiVolsi V. Inherited Follicular Epithelial-Derived Thyroid Carcinomas: From Molecular Biology to Histological Correlates. Endocr Pathol. 2021;32(1):77-101. https://doi.org/10.1007/s12022-020-09661-y. PMID: 33495912; PMCID: PMC7960606.

Condello V, Roberts JW, Stenman A, Larsson C, Viswanathan K, Juhlin CC. Atrophic changes in thyroid tumors are strong indicators of underlying DICER1 mutations: a bi-institutional genotype-phenotype correlation study. Virchows Arch. 2024;485(1):105-114. https://doi.org/10.1007/s00428-024-03802-y. PMID: 38637342; PMCID: PMC11271315.

Jung CK, Liu Z, Hirokawa M, Bychkov A. Histological clues of DICER1 mutations in thyroid nodules. Virchows Arch. 2024;485(4):755-757. https://doi.org/10.1007/s00428-024-03915-4. PMID: 39231821.

Schiavo Lena M, Sánchez-Ares M, Brunetto E, Abdulkader-Nallib I, Maggiore R, Barbieri D, Vigone MC, Perticone F, Lanzi R, Presi S, Carrera P, Cangi MG, Arrigoni G, Doglioni C, Cameselle-Teijeiro JM. Focal High-Grade Areas with a Tumor-in-Tumor Pattern: Another Feature of Pediatric DICER1-Associated Thyroid Carcinoma? Endocr Pathol. 2025 May 31;36(1):20. https://doi.org/10.1007/s12022-025-09863-2. PMID: 40448797.

Juhlin CC, Mete O. Letter to the Editor: Morphological Indicators of DICER1 Mutations May Guide Somatic and Germline Testing. Thyroid. 2025;35(1):120-121. https://doi.org/10.1089/thy.2024.0556. PMID: 39714925.

Cameselle-García S, Abdulkader-Nallib I, Sánchez-Ares M, Cameselle-Teijeiro JM. Cribriform morular thyroid carcinoma: Clinicopathological and molecular basis for both a preventive and therapeutic approach for a rare tumor (Review). Oncol Rep. 2024;52(3):119. https://doi.org/10.3892/or.2024.8778. PMID: 39027989; PMCID: PMC11292300.

Garrido-Gil P, Fernandez-Rodríguez P, Rodríguez-Pallares J, Labandeira-Garcia JL. Laser capture microdissection protocol for gene expression analysis in the brain. Histochem Cell Biol.;148(3):299–311. https://doi.org/10.1007/s00418-017-1585-1. PMID: 28560490.

Horak P, Griffith M, Danos AM, Pitel BA, Madhavan S, Liu X, Chow C, Williams H, Carmody L, Barrow-Laing L, Rieke D, Kreutzfeldt S, Stenzinger A, Tamborero D, Benary M, Rajagopal PS, Ida CM, Lesmana H, Satgunaseelan L, Merker JD, Tolstorukov MY, Campregher PV, Warner JL, Rao S, Natesan M, Shen H, Venstrom J, Roy S, Tao K, Kanagal-Shamanna R, Xu X, Ritter DI, Pagel K, Krysiak K, Dubuc A, Akkari YM, Li XS, Lee J, King I, Raca G, Wagner AH, Li MM, Plon SE, Kulkarni S, Griffith OL, Chakravarty D, Sonkin D. Standards for the classification of pathogenicity of somatic variants in cancer (oncogenicity): Joint recommendations of Clinical Genome Resource (ClinGen), Cancer Genomics Consortium (CGC), and Variant Interpretation for Cancer Consortium (VICC). Genet Med. 2022;24(5):986-998. https://doi.org/10.1016/j.gim.2022.01.001. Erratum in: Genet Med. 2022;24(9):1991. https://doi.org/10.1016/j.gim.2022.07.001. PMID: 35101336; PMCID: PMC9081216.

Nosé V, Gill A, Teijeiro JMC, Perren A, Erickson L. Overview of the 2022 WHO Classification of Familial Endocrine Tumor Syndromes. Endocr Pathol. 2022;33(1):197-227. https://doi.org/10.1007/s12022-022-09705-5. PMID: 35285003.

Onder S, Mete O, Yilmaz I, Bayram A, Bagbudar S, Altay AY, Issin G, Terzi NK, Iscan Y, Sormaz IC, Tunca F, Senyurek YG, Yegen G. DICER1 Mutations Occur in More Than One-Third of Follicular-Patterned Pediatric Papillary Thyroid Carcinomas and Correlate with a Low-Risk Disease and Female Gender Predilection. Endocr Pathol. 2022;33(4):437-445. https://doi.org/10.1007/s12022-022-09736-y. PMID: 36251117.

Mastnikova K, Bulanova Pekova B, Kuklikova V, Vaclavikova E, Carkova J, Katra R, Fialova L, Vlcek P, Kodetova D, Chovanec M, Drozenova J, Matej R, Pacesova P, Novak Z, Procykova K, Vcelak J, Bendlova B. DICER1 Variants in Pediatric and Young Adult Thyroid Nodules. Thyroid. 2024 Oct;34(10):1225-1233. https://doi.org/10.1089/thy.2024.0188. Epub 2024 Sep 27. PMID: 39283830.

Gullo I, Batista R, Rodrigues-Pereira P, Soares P, Barroca H, do Bom-Sucesso M, Sobrinho-Simões M. Multinodular Goiter Progression Toward Malignancy in a Case of DICER1 Syndrome: Histologic and Molecular Alterations. Am J Clin Pathol. 2018;149(5):379–386. https://doi.org/10.1093/ajcp/aqy004. PMID: 29538609.

Shin SH, Yoon JH, Son MH, Kim SJ, Park SY, Kim HY, Lee HS, Park HJ, Park BK. Follicular thyroid carcinoma arising after hematopoietic stem cell transplantation in a child with pleuropulmonary blastoma. Thyroid. 2012 May;22(5):547-51. https://doi.org/10.1089/thy.2011.0161. Epub 2012 Apr 2. PMID: 22468940.

Wasserman JD, Sabbaghian N, Fahiminiya S, Chami R, Mete O, Acker M, Wu MK, Shlien A, de Kock L, Foulkes WD. DICER1 Mutations Are Frequent in Adolescent-Onset Papillary Thyroid Carcinoma. J Clin Endocrinol Metab. 2018 May 1;103(5):2009-2015. https://doi.org/10.1210/jc.2017-02698. Erratum in: J Clin Endocrinol Metab. 2018 Aug 1;103(8):3114. https://doi.org/10.1210/jc.2018-01190. PMID: 29474644.

Lengyel K, Lubin DJ, Hsiao WY, Sirotnikov S, Luo G, Roberts JW, Shi Q, Magliocca K, Lewis MM, Sears DL, Ilyas G, Rogers BB, Viswanathan K. Comprehensive evaluation of cytomorphologic, histologic, and molecular features of DICER1-altered thyroid lesions on FNA: A multipractice experience. Cancer Cytopathol. 2024 Jun;132(6):359-369. https://doi.org/10.1002/cncy.22805. Epub 2024 Mar 23. PMID: 38520219.

Whaley RD, Gupta S, Manninen MC, O'Brien DR, Erickson LA. Clinicopathologic and Molecular Analysis of 15 Pediatric and Young Adult Patients with High-Grade Non-anaplastic Thyroid Carcinoma. Endocr Pathol. 2024;35(4):397-410. https://doi.org/10.1007/s12022-024-09842-z. PMID: 39636536.

Juhlin CC, Stenman A, Zedenius J. Macrofollicular variant follicular thyroid tumors are DICER1 mutated and exhibit distinct histological features. Histopathology. 2021;79(4):661-666. https://doi.org/10.1111/his.14416. PMID: 34008223.

Agaimy A, Nosé V, Sobrinho-Simões M. Thyroblastoma. In: WHO Classification of Tumours Editorial Board. Endocrine and neuroendocrine tumours. Lyon (France): International Agency for Research on Cancer; 2025. (WHO classification of tumours series, 5th ed.; vol. 10). https://publications.iarc.who.int/645.

de Kock L, Bah I, Revil T, Bérubé P, Wu MK, Sabbaghian N, Priest JR, Ragoussis J, Foulkes WD. Deep Sequencing Reveals Spatially Distributed Distinct Hot Spot Mutations in DICER1-Related Multinodular Goiter. J Clin Endocrinol Metab. 2016 Oct;101(10):3637-3645. https://doi.org/10.1210/jc.2016-1328. Epub 2016 Jul 26. PMID: 27459524.

Erickson LA, Mete O, Cameselle-Teijeiro JM, LiVolsi V, Nosé V, Sobrinho-Simões M, Jung CK. Cribriform-morular thyroid carcinoma. In: WHO Classification of Tumours Editorial Board. Endocrine and neuroendocrine tumours. Lyon (France): International Agency for Research on Cancer; 2025. (WHO classification of tumours series, 5th ed.; vol. 10). https://publications.iarc.who.int/645.

Yanagawa N, Uesugi N, Nishiya M, Sugimoto R, Osakabe M, Saitoh H, Maemondo M, Sugai T. Morphological and Molecular Characteristics in Low Grade Fetal Adenocarcinoma of the Lung: Two Case Reports and Literature Review. Int J Surg Pathol. 2022;30(7):797-803. https://doi.org/10.1177/10668969221081741. PMID: 35188818.

Tanaka Y, Kato K, Notohara K, Nakatani Y, Miyake T, Ijiri R, Nishimata S, Ishida Y, Kigasawa H, Ohama Y, Tsukayama C, Kobayashi Y, Horie H. Significance of aberrant (cytoplasmic/nuclear) expression of beta-catenin in pancreatoblastoma. J Pathol. 2003;199(2):185-90. https://doi.org/10.1002/path.1262. PMID: 12533831.

Sarlin JG, Mori K. Morules in epithelial tumors of the colon and rectum. Am J Surg Pathol. 1984;8(4):281-5. https://doi.org/10.1097/00000478-198404000-00005. PMID: 6711738.

Mochizuki K, Kondo T, Oishi N, Tahara I, Inoue T, Kasai K, Nakazawa T, Katoh R. Squamous morula formation in colorectal adenoma: Immunohistochemical and molecular analyses. Pathol Res Pract. 2015;211(10):797-800. https://doi.org/10.1016/j.prp.2015.05.002. PMID: 26298635.

Houghton O, Connolly LE, McCluggage WG. Morules in endometrioid proliferations of the uterus and ovary consistently express the intestinal transcription factor CDX2. Histopathology. 2008;53(2):156-65. https://doi.org/10.1111/j.1365-2559.2008.03083.x. PMID: 18752499.

Cameselle-Teijeiro J, Alberte-Lista L, Chiarelli S, Buriticá C, Gonçalves L, González-Cámpora R, Nogales FF. CD10 is a characteristic marker of tumours forming morules with biotin-rich, optically clear nuclei that occur in different organs. Histopathology. 2008;52(3):389-92. https://doi.org/10.1111/j.1365-2559.2007.02911.x. PMID: 18081818.

Cameselle-Teijeiro JM, Peteiro-González D, Caneiro-Gómez J, Sánchez-Ares M, Abdulkader I, Eloy C, Melo M, Amendoeira I, Soares P, Sobrinho-Simões M. Cribriform-morular variant of thyroid carcinoma: a neoplasm with distinctive phenotype associated with the activation of the WNT/β-catenin pathway. Mod Pathol. 2018;31(8):1168-1179. https://doi.org/10.1038/s41379-018-0070-2. PMID: 29785019.

Boyraz B, Sadow PM, Asa SL, Dias-Santagata D, Nosé V, Mete O. Cribriform-Morular Thyroid Carcinoma Is a Distinct Thyroid Malignancy of Uncertain Cytogenesis. Endocr Pathol. 2021;32(3):327-335. https://doi.org/10.1007/s12022-021-09683-0. PMID: 34019236; PMCID: PMC9353615.

Dettmer MS, Hürlimann S, Scheuble L, Vassella E, Perren A, Wicke C. Cribriform Morular Thyroid Carcinoma - Ultimobranchial Pouch-Related? Deep Molecular Insights of a Unique Case. Endocr Pathol. 2023 Sep;34(3):342-348. https://doi.org/10.1007/s12022-023-09775-z. PMID: 37249797; PMCID: PMC10511600.

Echegoyen-Silanes A, Pineda-Arribas JJ, Sánchez-Ares M, Cameselle-García S, Sobrino B, Ruíz-Ponte C, Piso-Neira M, Anda E, Cameselle-Teijeiro JM. Cribriform morular thyroid carcinoma: a case report with pathological, immunohistochemical, and molecular findings suggesting an origin from follicular cells (or their endodermal precursors). Virchows Arch. 2023 Mar;482(3):615–623. https://doi.org/10.1007/s00428-023-03495-9. Epub 2023 Jan 23. PMID: 36689061; PMCID: PMC10033468.

Faizo NL. The intestinal stem cell as a target: A review. Medicine (Baltimore). 2024;103(34):e39456. https://doi.org/10.1097/MD.0000000000039456. PMID: 39183418; PMCID: PMC11346866.

Sherwood RI, Maehr R, Mazzoni EO, Melton DA. Wnt signaling specifies and patterns intestinal endoderm. Mech Dev. 2011;128(7-10):387-400. https://doi.org/10.1016/j.mod.2011.07.005. PMID: 21854845; PMCID: PMC3223331.

de Kock L, Bah I, Wu Y, Xie M, Priest JR, Foulkes WD. Germline and Somatic DICER1 Mutations in a Well-Differentiated Fetal Adenocarcinoma of the Lung. J Thorac Oncol. 2016;11(3):e31-3. https://doi.org/10.1016/j.jtho.2015.09.012. PMID: 26886166.

Saad AG, Kumar S, Ron E, Lubin JH, Stanek J, Bove KE, Nikiforov YE. Proliferative activity of human thyroid cells in various age groups and its correlation with the risk of thyroid cancer after radiation exposure. J Clin Endocrinol Metab. 2006 Jul;91(7):2672-7. https://doi.org/10.1210/jc.2006-0417. Epub 2006 May 2. PMID: 16670159.

Saliba M, Alzumaili BA, Katabi N, Dogan S, Tuttle RM, Zoltan A, Pandit-Taskar N, Xu B, Ghossein RA. Clinicopathologic and Prognostic Features of Pediatric Follicular Cell-derived Thyroid Carcinomas: A Retrospective Study of 222 Patients. Am J Surg Pathol. 2022 Dec 1;46(12):1659–1669. https://doi.org/10.1097/PAS.0000000000001958. Epub 2022 Aug 29. PMID: 36040037; PMCID: PMC9669120.

Ver Berne J, Van den Bruel A, Vermeire S, De Paepe P. DICER1 Mutations Define the Landscape of Poorly Differentiated Thyroid Carcinoma in Children and Young Adults: Case Report and Literature Review. Am J Surg Pathol. 2024 Oct 1;48(10):1277-1283. https://doi.org/10.1097/PAS.0000000000002265. Epub 2024 Jun 24. PMID: 38912716.

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