Thyroid Carcinomas That Occur in Familial Adenomatous Polyposis Patients Recurrently Harbor Somatic Variants inAPC,BRAF, andKTM2D

Nieminen, Taina T.; Walker, Christopher J.; Olkinuora, Alisa; Genutis, Luke K.; O’Malley, Margaret; Wakely, Paul E.; LaGuardia, Lisa; Koskenvuo, Laura; Arola, Johanna; Lepistö, Anna; Brock, Pamela; Yilmaz, Ayse Selen; Eisfeld, Ann‐Kathrin; Church, James M.; Peltomäki, Païvi; Chapelle, Albert de la

doi:10.1089/thy.2019.0561

Cited by 22 publications

(30 citation statements)

References 45 publications

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“…The thyroid tumor associated with FAP is the cribriform-morular variant of PTC, more recently designated as cribriform-morular variant of thyroid carcinoma [ 134 , 135 ]. The prevalence of the cribriform-morular variant (C-MV) of TC among FAP patients reaches up to 16% when ultrasonographic screening is combined with fine needle aspiration biopsy (FNAB) [ 136 ], and this is more common in young women (mean age 26 years, range 8–61 years, with a ratio women/men of 61:1, respectively) [ 134 , 137 , 138 ]. In these families the diagnosis of C-MV of TC precedes that of FAP in up to 40% of the cases [ 134 ].…”

Section: Syndromic Familial Non-medullary Thyroid Carcinoma (Sfnmtc)mentioning

confidence: 99%

“…In attenuated FAP, associated inherited mutations are located nearer the N-terminus or within the alternatively spliced section of exon 9 [ 128 ]. In more than 80% of patients with FAP and thyroid cancer, APC germline gene mutations occur between codons 140 and 1513 (largely outside the MCR) [ 137 , 138 , 156 , 157 ]. Most APC germline mutations associated with thyroid cancer occur in the 5′-portion of exon 15, in the same genomic area associated with CHRPE (codons 463–1387), and codon 1061 is also a hot spot for both C-MV of TC and hepatoblastoma [ 158 ].…”

Section: Syndromic Familial Non-medullary Thyroid Carcinoma (Sfnmtc)mentioning

confidence: 99%

“…TERT promotor mutation has been reported in a sporadic case with aggressive behavior [ 151 ]. Rare somatic mutations in thyroid tumors such as in the KMT2C and KMT2D genes have been described in 1 and 4 cases of C-MV of TC, respectively, coexisting with the germline mutation of the APC gene [ 138 ]. In this same series of patients with FAP and thyroid tumors, BRAF V600E somatic mutations have been detected in conventional PTCs but not in the cases displaying a C-MV phenotype [ 138 ].…”

Section: Syndromic Familial Non-medullary Thyroid Carcinoma (Sfnmtc)mentioning

confidence: 99%

“…[ 136 ]. Somatic mutations in RAS , PIK3CA , KMT2C , and/or BRAF V600E , as well as somatic RET/PTC rearrangements could act as a somatic “second-hit” in the development of other forms of thyroid cancers in affected individuals [ 9 , 134 , 138 ]. A tumor growth-promoting role has been attributed to the sex hormones due to the striking predominance of C-MV of TC in women and the strong expression of estrogen and progesterone receptors by tumor cells.…”

Section: Syndromic Familial Non-medullary Thyroid Carcinoma (Sfnmtc)mentioning

confidence: 99%

“…Tumor cells are always positive for TTF1 (f). Nuclear and cytoplasmic positivity for β-catenin is the hallmark of the cribriform-morular variant of thyroid carcinoma (e) outside the MCR) [137,138,156,157]. Most APC germline mutations associated with thyroid cancer occur in the 5′-portion of exon 15, in the same genomic area associated with CHRPE (codons 463-1387), and codon 1061 is also a hot spot for both C-MV of TC and hepatoblastoma [158].…”

Section: Genetic Featuresmentioning

confidence: 99%

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Inherited Follicular Epithelial-Derived Thyroid Carcinomas: From Molecular Biology to Histological Correlates

et al. 2021

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Cancer derived from thyroid follicular epithelial cells is common; it represents the most common endocrine malignancy. The molecular features of sporadic tumors have been clarified in the past decade. However the incidence of familial disease has not been emphasized and is often overlooked in routine practice. A careful clinical documentation of family history or familial syndromes that can be associated with thyroid disease can help identify germline susceptibility-driven thyroid neoplasia. In this review, we summarize a large body of information about both syndromic and non-syndromic familial thyroid carcinomas. A significant number of patients with inherited non-medullary thyroid carcinomas manifest disease that appears to be sporadic disease even in some syndromic cases. The cytomorphology of the tumor(s), molecular immunohistochemistry, the findings in the non-tumorous thyroid parenchyma and other associated lesions may provide insight into the underlying syndromic disorder. However, the increasing evidence of familial predisposition to non-syndromic thyroid cancers is raising questions about the importance of genetics and epigenetics. What appears to be “sporadic” is becoming less often truly so and more often an opportunity to identify and understand novel genetic variants that underlie tumorigenesis. Pathologists must be aware of the unusual morphologic features that should prompt germline screening. Therefore, recognition of harbingers of specific germline susceptibility syndromes can assist in providing information to facilitate early detection to prevent aggressive disease.

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Section: Syndromic Familial Non-medullary Thyroid Carcinoma (Sfnmtc)mentioning

confidence: 99%

Section: Syndromic Familial Non-medullary Thyroid Carcinoma (Sfnmtc)mentioning

confidence: 99%

Section: Syndromic Familial Non-medullary Thyroid Carcinoma (Sfnmtc)mentioning

confidence: 99%

Section: Syndromic Familial Non-medullary Thyroid Carcinoma (Sfnmtc)mentioning

confidence: 99%

Section: Genetic Featuresmentioning

confidence: 99%

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Inherited Follicular Epithelial-Derived Thyroid Carcinomas: From Molecular Biology to Histological Correlates

et al. 2021

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Molecular Pathology of Endocrine Tumors

Erickson

2023

Molecular Surgical Pathology

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Cribriform morular thyroid carcinoma: a case report with pathological, immunohistochemical, and molecular findings suggesting an origin from follicular cells (or their endodermal precursors)

Echegoyen-Silanes

Pineda-Arribas²,

Sánchez‐Ares

et al. 2023

Virchows Arch

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Cribriform morular thyroid carcinoma (CMTC) is a rare malignant thyroid tumor with a peculiar growth pattern secondary to permanent activation of the WNT/β-catenin pathway. CMTC may be associated with familial adenomatous polyposis or sporadic; it shares morphological features with papillary thyroid carcinoma (PTC) and was considered a variant of PTC in the 2017 WHO classification of tumors of endocrine organs. The new 5th edition of the WHO classification of endocrine and neuroendocrine tumors considered CMTC an independent thyroid neoplasm of uncertain histogenesis. A thymic/ultimobranchial pouch-related differentiation in CMTC has been recently postulated. We, however, have used the pathological and immunohistochemical features of this case of CMTC with 2 novel oncogenic somatic variants (c.3428_3429insA, p.(Tyr1143Ter) and c.3565del, p. (Ser1189Hisfs*76) of the APC gene to propose an origin from follicular cells (or their endodermal precursors). As usual in CMTC, the morular component of this tumor was positive for CDX2. Given the fact that WNT/β-catenin signaling, through CDX2, activates large intestine and small intestine gene expression, we postulate that in CMTC, the tumor cells have their terminal differentiation blocked, thus showing a peculiar primitive endodermal (intestinal-like) phenotype negative for sodium-iodide symporter, thyroperoxidase, and thyroglobulin. Establishing the histogenesis of CMTC is very relevant for the development of appropriate therapies of redifferentiation, particularly in patients where the tumor cannot be controlled by surgery.

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Thyroid Carcinomas That Occur in Familial Adenomatous Polyposis Patients Recurrently Harbor Somatic Variants inAPC,BRAF, andKTM2D

Cited by 22 publications

References 45 publications

Inherited Follicular Epithelial-Derived Thyroid Carcinomas: From Molecular Biology to Histological Correlates

Inherited Follicular Epithelial-Derived Thyroid Carcinomas: From Molecular Biology to Histological Correlates

Molecular Pathology of Endocrine Tumors

Cribriform morular thyroid carcinoma: a case report with pathological, immunohistochemical, and molecular findings suggesting an origin from follicular cells (or their endodermal precursors)

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