Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Department of Pathology and Laboratory Medicine, Children's Healthcare of Atlanta, Atlanta, GA, USA.
Virchows Arch. 2024 Jul;485(1):105-114. doi: 10.1007/s00428-024-03802-y. Epub 2024 Apr 19.
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.
体细胞和双等位基因 DICER1 突变已在甲状腺肿瘤的亚组中报道，支持该基因在甲状腺肿瘤发生中的作用。由于最近的研究引起了人们对巨滤泡模式、萎缩性改变和乳头状结构与 DICER1 突变相关的关注，我们试图在一个双机构队列中探索这些观察结果。共对 61 个甲状腺病变（54 个肿瘤和 7 个甲状腺滤泡性结节性疾病病例；TFND）进行了组织学再检查和临床随访，其中包括 26 个 DICER1 突变和 35 个 DICER1 野生型对照。DICER1 突变病变与手术时年龄较小（29.2±12.5 岁 vs 51.3±18.8 岁，p=0.0001）、主要巨滤泡生长模式（26 例突变病例中的 20 例 vs 35 例野生型中的 18 例；p=0.01）和萎缩性改变（26 例突变病例中的 20 例 vs 35 例野生型中的 2 例；p=0.0001）有统计学显著关联。当排除 TFND 病例时，也得到了相似的结果。我们还提出了甲状腺病变 DICER1 测序的临床和组织学分类标准，这导致在随访中确定了 26 例中的 16 例（62%）存在 DICER1 变体。其中，12 例中有可用数据的 3 例被发现携带一种 DICER1 种系突变。这一观察结果表明，大多数 DICER1 突变是体细胞突变——但这意味着对种系组织进行测序可能具有临床意义。我们得出结论，DICER1 突变聚集在具有巨滤泡模式的年轻肿瘤患者中，最显著的是萎缩性改变。鉴于种系受累的比率，我们的发现可能具有临床价值，使病理学家能够根据组织学发现对病例进行基因检测的分类。
