Atrophic changes in thyroid tumors are strong indicators of underlying DICER1 mutations: a bi-institutional genotype-phenotype correlation study.
DICER1
Atrophic changes
Macrofollicular pattern
Somatic mutation
Journal
Virchows Archiv : an international journal of pathology
ISSN: 1432-2307
Titre abrégé: Virchows Arch
Pays: Germany
ID NLM: 9423843
Informations de publication
Date de publication:
19 Apr 2024
19 Apr 2024
Historique:
received:
11
03
2024
accepted:
05
04
2024
revised:
26
03
2024
medline:
19
4
2024
pubmed:
19
4
2024
entrez:
18
4
2024
Statut:
aheadofprint
Résumé
Somatic and biallelic DICER1 mutations are reported in subsets of thyroid tumors, supporting the role of this gene in thyroid tumor development. As recent studies have brought attention to macrofollicular patterns, atrophic changes, and papillary structures as being associated with DICER1 mutations, we sought to explore these observations in a bi-institutional cohort. A total of 61 thyroid lesions (54 tumors and 7 cases of thyroid follicular nodular disease; TFND), including 26 DICER1 mutated and 35 DICER1 wildtype controls were subjected to histological re-investigation and clinical follow-up. DICER1-mutated lesions showed a statistically significant association with younger age at surgery (29.2 ± 12.5 versus 51.3 ± 18.8, p = 0.0001), a predominant macrofollicular growth pattern (20/26 mutated cases versus 18/35 wildtype; p = 0.01) and atrophic changes (20/26 mutated cases versus 2/35 wildtype; p = 0.0001). Similar results were obtained when excluding TFND cases. We also present clinical and histological triaging criteria for DICER1 sequencing of thyroid lesions, which led to the identification of DICER1 variants in 16 out of 26 cases (62%) when followed. Among these, 3 out of 12 cases with available data were found to carry a constitutional DICER1 mutation. This observation suggests that the majority of DICER1 mutations are somatic-however implies that sequencing of constitutional tissues could be clinically motivated. We conclude that DICER1 mutations are amassed in younger patients with macrofollicular-patterned tumors and, most strikingly, atrophic changes. Given the rate of constitutional involvement, our findings could be of clinical value, allowing the pathologist to triage cases for genetic testing based on histological findings.
Identifiants
pubmed: 38637342
doi: 10.1007/s00428-024-03802-y
pii: 10.1007/s00428-024-03802-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Cancerfonden
ID : CAN 2020/426
Informations de copyright
© 2024. The Author(s).
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