Cribriform-morular Thyroid Carcinoma Arising in a Medulloblastoma Survivor: Two Metachronous Tumors Shared with the Activation of the Wnt Signaling Pathway
Restricted accessResearch articleFirst published online December, 2024
Cribriform-morular Thyroid Carcinoma Arising in a Medulloblastoma Survivor: Two Metachronous Tumors Shared with the Activation of the Wnt Signaling Pathway
Wnt signaling pathway activation is involved in the pathogenesis of a series of malignant tumors and is characterized by the nuclear accumulation of β-catenin protein. The occurrence of two or more Wnt pathway-associated tumors in a single individual is uncommon and generally attributed to inherited cancer syndrome, especially familial adenomatous polyposis (FAP). Herein, we presented a rare case of a child who suffered from the occurrence of Wnt-activated medulloblastoma and cribriform-morular thyroid carcinoma (CMTC) within a 9-year interval. She had no history of FAP and harbored an unexpected somatic mutation of the APC gene in the CMTC tumor. The potential agents involved in the pathogenesis of the two molecular-linked tumors other than FAP were discussed in this report.
LouisDNPerryAWesselingP, et al.The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro Oncol. 2021;23(8):1231-1251.
2.
PietschTSchmidtRRemkeM, et al.Prognostic significance of clinical, histopathological, and molecular characteristics of medulloblastomas in the prospective HIT2000 multicenter clinical trial cohort. Acta Neuropathol. 2014;128(1):137-149.
3.
NorthcottPABuchhalterISorana MorrissyA, et al.The whole-genome landscape of medulloblastoma subtypes. Nature. 2017;547(7663):311-317.
4.
WaszakSMNorthcottPABuchhalterI, et al.Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort. Lancet Oncol. 2018;19(6):785-798.
5.
Christofer JuhlinCMeteOBalochZW. The 2022 WHO classification of thyroid tumors: novel concepts in nomenclature and grading. Endocr Relat Cancer. 2022;30(2):e220293.
6.
Manuel Cameselle-TeijeiroJPeteiro-GonzálezDCaneiro-GómezJ, et al.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.
7.
OkamotoYKashimaKDaaT, et al.Morule with biotincontaining intranuclear inclusions in thyroid carcinoma. Pathol Int. 1995;45(8):573-579.
8.
Manuel Cameselle-TeijeiroJMeteOAsaSL, et al.Inherited follicular epithelial-derived thyroid carcinomas: from molecular biology to histological correlates. Endocr Pathol. 2021;32(1):77-101.
9.
AydemirliMDvan der TuinKHesFJ, et al.A unique case of two somatic APC mutations in an early onset cribriform-morular variant of papillary thyroid carcinoma and overview of the literature. Fam Cancer. 2020;19(1):15-21.
10.
XuBYoshimotoKMiyauchiA, et al.Cribriform-morular variant of papillary thyroid carcinoma: a pathological and molecular genetic study with evidence of frequent somatic mutations in exon 3 of the beta-catenin gene. J Pathol. 2003;199(1):58-67.
11.
ZhangYWangX. Targeting the Wnt/β-catenin signaling pathway in cancer. J Hematol Oncol. 2020;13(1):165.
12.
YuFYuCLiF, et al.Wnt/β-catenin signaling in cancers and targeted therapies. Signal Transduct Target Ther. 2021;6(1):307.
13.
JiLLuBZamponiR, et al.USP7 inhibits Wnt/β-catenin signaling through promoting stabilization of Axin. Nat Commun. 2019;10(1):4184.
14.
EllisonDWDaltonJKocakM, et al.Medulloblastoma: clinicopathological correlates of SHH, WNT, and non-SHH/WNT molecular subgroups. Acta Neuropathol. 2011;121(3):381-396.
15.
KaurKKakkarAKumarA, et al.Integrating molecular subclassification of medulloblastomas into routine clinical practice: a simplified approach. Brain Pathol. 2016;26(3):334-343.
16.
BalochZWAsaSLBarlettaJA, et al.Overview of the 2022 WHO classification of thyroid neoplasms. Endocr Pathol. 2022;33(1):27-63.
17.
FentonPAClarkeSEOwenW, et al.Cribriform variant papillary thyroid cancer: a characteristic of familial adenomatous polyposis. Thyroid. 2001;11(2):193-197.
18.
NieminenTTWalkerCJOlkinuoraA, et al.Thyroid carcinomas that occur in familial AdenomatousPolyposis patients recurrently harbor somatic variants in APC, BRAF, and KTM2D. Thyroid. 2020;30(3):380-388.
JansenAMLGoelA. Mosaicism in patients with colorectal cancer or polyposis syndromes: a systematic review. Clin Gastroenterol Hepatol. 2020;18(9):1949-1960.
21.
RofesPGonzálezSNavarroM, et al.Paired somatic-germline testing of 15 polyposis and colorectal cancer-predisposing genes highlights the role of APC mosaicism in de Novo familial adenomatous polyposis. J Mol Diagn. 2021;23(11):1452-1459.
22.
SieberOMSegditsasSKnudsenAL, et al.Disease severity and genetic pathways in attenuated familial adenomatous polyposis vary greatly but depend on the site of the germline mutation. Gut. 2006;55(10):1440-1448.
23.
AneleCCMartinIDugganMMP, et al.Attenuated familial adenomatous polyposis: a phenotypic diagnosis but obsolete term?Dis Colon Rectum. 2022;65(4):529-535.
24.
RoncucciLPedroniMMarianiF. Attenuated adenomatous polyposis of the large bowel: present and future. World J Gastroenterol. 2017;23(23):4135-4139.
25.
LiuQLiXLiS, et al.Three novel mutations of APC gene in Chinese patients with familial adenomatous polyposis. Tumour Biol. 2016;37(8):11421-11427.
26.
PradhanDSharmaAMohantySK, et al.Cribriform-morular variant of papillary thyroid carcinoma. Pathol Res Pract. 2015;211(10):712-716.
27.
AkaishiJKondoTSuginoK, et al.Cribriform-morular variant of papillary thyroid carcinoma: clinical and pathological features of 30 cases. World J Surg. 2018;42(11):3616-3623.
28.
Cameselle-TeijeiroJRuiz-PonteCLoidiL, et al.Somatic but not germline mutation of the APC gene in a case of cribriform-morular variant of papillary thyroid carcinoma. Am J Clin Pathol. 2001;115(4):486-493.
29.
NakazawaTCelestinoRMachadoJC, et al.Cribriform-Morular variant of papillary thyroid carcinoma displaying poorly differentiated features. Int J Surg Pathol. 2013;21(4):379-389.
DaviesSM. Subsequent malignant neoplasms in survivors of childhood cancer: childhood cancer survivor study (CCSS) studies. Pediatr Blood Cancer. 2007;48(7):727-730.
32.
BavleATewariSSissonA, et al.Meta-analysis of the incidence and patterns of second neoplasms after photon craniospinal irradiation in children with medulloblastoma. Pediatr Blood Cancer. 2018;65(8):e27095.
33.
ShiehJTPenon-PortmannMWongKHY, et al.Application of full-genome analysis to diagnose rare monogenic disorders. NPJ Genom Med. 2021;6(1):77.
34.
Levy-SakinMPastorSMostovoyY, et al.Genome maps across 26 human populations reveal population-specific patterns of structural variation. Nat Commun. 2019;10(1):1025.
35.
WongKHYLevy-SakinMKwokPY. De novo human genome assemblies reveal spectrum of alternative haplotypes in diverse populations. Nat Commun. 2018;9(1):3040.
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