Overview of the 2022 WHO Classification of Familial Endocrine Tumor Syndromes

Nosé, Vânia; Gill, Anthony J.; Cameselle-Teijeiro, José; Perren, Aurel; Erickson, Lori A.

doi:10.1007/s12022-022-09705-5

Cited by 35 publications

(49 citation statements)

References 264 publications

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“…The role of germline pathogenic DICER1 variants in the development of both benign and malignant follicular cell thyroid neoplasms has now been well-established in the setting of DICER1 syndrome [17,18]. The estimated risk for developing differentiated thyroid carcinoma is 16-to 24-fold whereas developing multifocal benign follicular cell-derived thyroid tumors (e.g., follicular nodular disease and follicular adenomas) by age 40 is 75% for females and 17% for males in affected patients with germline pathogenic variants [32].…”

Section: Discussionmentioning

confidence: 99%

“…A recently defined embryonal malignant thyroid neoplasm "thyroblastoma (WHO 2022)" has also been linked to somatic DICER1 variants [18,36]. Despite the lack of well-established link to germline pathogenic DICER1 variants, such a diagnosis still triggers exclusion of underlying germline pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…As in adults, papillary thyroid carcinoma is the most common histologic type of pediatric follicular cell-derived thyroid carcinoma [1,2]. Despite morphologic similarities, pediatric papillary thyroid carcinomas (PPTCs) differ from their adult counterparts [2][3][4] with respect to genomic alterations (e.g., high prevalence of oncogene fusions, overall lower frequency of BRAF p.V600E and RAS-mutations, universally reported absence with only exceptional occurrence of TERT promoter mutations, increased frequency of inherited neoplasia associated somatic and/or germline pathogenic variants) and distinct clinical and pathological features (e.g., higher frequency for lymph node and/or distant metastases, ionizing radiation-induced pathogenesis, better overall prognosis compared to adults with similar features, lower fraction of tall cell PTC, and higher frequency of diffuse sclerosing PTC) [1,[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. These observations have made PPTC an area of continued interest in thyroid neoplasia.…”

Section: Introductionmentioning

confidence: 99%

“…13, and encodes a ribonuclease (RNase) IIIb protein which plays a central regulator role in the miRNA processing [22]. The discovery of germline pathogenic DICER1 variants as the cause of DICER1 syndrome and better understanding of the spectrum of DICER1 syndrome-related endocrine manifestations [2,17,18,[23][24][25] have also triggered the expansion of somatic DICER1-driven thyroid disease in both pediatric and adult thyroid nodules [5][6][7][8][26][27][28][29][30]. DICER1-related pediatric thyroid disease consists of benign follicular nodular disease and follicular adenoma [6][7][8] and differentiated thyroid carcinomas [5][6][7][8], as well as some poorly differentiated thyroid carcinomas [6,30].…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2022

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Some pediatric papillary thyroid carcinoma (PPTC) cohorts have suggested a preliminary correlation with respect to DICER1 mutation status and histomorphology in both benign and malignant follicular cell-derived nodules; however, the data regarding correlates of DICER1-related sporadic PPTCs subtyped based on the 2022 WHO classification criteria are largely unavailable. The current study investigated the status of hotspot DICER1 mutations with clinical, histological and outcome features in a series of 56 patients with PPTCs with no clinical or family history of DICER1-related syndromic manifestation. Fifteen (27%) PPTCs harbored BRAF p.V600E. Eight (14%) cases of PPTCs harbored DICER1 mutations with no associated BRAF p.V600E. DICER1 mutations were identified in exons 26 and 27. A novel D1810del (c.5428_5430delGAT) mutation was also detected. We also confirmed the absence of hotspot DICER1 mutations in the matched non-tumor tissue DNA in all 8 DICER1-related PPTCs. The mean age of DICER1-harboring PPTCs was 15.1 (range: 9-18) years whereas the rest of this cohort had a mean age of 14.8 (range 6-18) years. With the exception of one PPTC, all DICER1-related PPTCs were seen in females (female-to-male ratio: 7). The female to male ratio was 3.8 in 48 DICER1-wild type PPTCs. In terms of histological correlates, 5 of 8 (63%) DICER1-mutant PPTCs were invasive encapsulated follicular variant papillary thyroid carcinomas (FVPTCs) including 4 minimally invasive FVPTCs and 1 encapsulated angioinvasive FVPTC, whereas the remaining 3 PPTCs were infiltrative classic papillary thyroid carcinomas (p < 0.05). The incidence of DICER1 mutations was 19.5% in BRAF p.V600E-wild type PPTCs. Sixty-three percent of DICER1 hotspot mutations occurred in invasive encapsulated FVPTCs, and this figure represents 38% of invasive encapsulated FVPTCs. Only one (12%) patient with DICER1-related disease showed a single lymph node with micro-metastasis. Unlike DICER1-wild type patients, no distant metastasis is identified in patients with DICER1-related PPTCs. The current series expands on the surgical epidemiology of somatic DICER1related PPTCs by correlating the mutation status with the clinicopathological variables. Our findings underscore that female gender predilection and enrichment in low-risk follicular-patterned PTCs are characteristics of DICER1-related PPTCs. KeywordsDICER1 • Follicular adenoma • Follicular nodular disease • Multinodular hyperplasia • Differentiated thyroid carcinoma • Papillary thyroid carcinoma • Pediatric thyroid carcinoma • Pediatric papillary thyroid carcinoma • BRAF p.V600E * Semen Onder

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

et al. 2022

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“…[3][4][5] Subsequently, familial syndromes affecting 1 endocrine organ were validated by recurrent underlying genetic alterations, including hyperparathyroidism (HPT)-jaw tumor syndrome (JT) and, more recently, MAFA-related familial insulinomatosis. 1,2 Endocrine neoplasms, across all organs, are challenging to diagnose and manage on multiple levels. First, they show variable histopathologic features with poor consensus on histopathologic features of malignancy.…”

mentioning

confidence: 99%

The Classic, the Trendy, and the Refashioned: A Primer for Pathologists on What Is New in Familial Endocrine Tumor Syndromes

Ababneh

Nosé

2022

Advances in Anatomic Pathology

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Familial endocrine tumor syndromes are continuously expanding owing to the growing role of genetic testing in routine clinical practice. Pathologists are usually the first on the clinical team to encounter these syndromes at their initial presentation; thus, recognizing them is becoming more pivotal in routine pathology practice to help in properly planning management and further family testing. Our increasing knowledge about them is reflected in the newer syndromes included in the new World Health Organization classification and in the evolving discovery of new endocrine tumors and new familial associations. In many of these syndromes, the clinical features and co-occurrence of multiple neoplasia are the only clues (multiple endocrine neoplasia syndromes). In other syndromes, specific morphologic findings (pituitary blastoma and DICER1 syndrome, cribriform morular thyroid carcinoma, and AFP syndrome) and available ancillary studies (SDHB in SDHdeficient tumor syndromes) can aid pathologists. The aim of this review is to provide a primer on recent updates on familial endocrine tumor syndromes and related tumors, focusing on recent classification changes or tumor syndromes where a clearer role for pathologists is at play.

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