ArticleEndocrine pathology2025
DICER1-Related Pediatric Thyroid Neoplasm with Follicular and Morular Growth: A Tumor that Did Not Read the Textbook.
Article in Endocrine pathology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Thyroid lesions associated with DICER1 syndrome include multifocal hyperplastic and benign neoplastic proliferations (follicular nodular disease) with characteristic macrofollicular and/or intrafollicular centripetal papillary growth patterns, frequently associated with atrophic and involutional changes. There are also well-differentiated thyroid carcinomas showing intermediate-type nuclei, sometimes combining high-grade areas (tumor-in-tumor pattern) and poorly differentiated carcinomas. Here, for the first time, we describe an encapsulated follicular cell thyroid tumor showing a mixed follicular and morular growth pattern, which presented in an 11-year-old girl with follicular nodular disease and a constitutional (germline) DICER1 p.(Tyr1357fs*18) pathogenic variant. The tumoral follicular component showed colloid and tumor cells with round nuclei, frequent chromatin clearing, and overlapping without grooves or pseudoinclusions (intermediate-type nuclei). There were scattered mitotic figures, but no tumor necrosis, infiltration, or vascular invasion. The morular structures lacked keratinization. The follicular areas were positive for TTF1/NKX2, PAX8, thyroglobulin, thyroperoxidase, keratin clones CKAE1/AE3 and 34bE12, CK19, and vimentin, whereas the morular component was positive for CKAE1/AE3, CK19, CD10, and CDX2. Aberrant (nuclear and cytoplasmic) immunolabeling pattern for β-catenin was limited to the morular structures. The Ki67 proliferation index was 21% in the follicular component and less than 1% in the morulae. In addition to the constitutional DICER1 p.(Tyr1357fs*18) variant, the somatic DICER1 p.(Asp1910Tyr) oncogenic variant and the somatic CTNNB1 p.(Thr41Ala) oncogenic variant were also identified in this tumor. This "DICER1-related pediatric thyroid neoplasm with follicular and morular growth" expands the spectrum of DICER1-associated thyroid lesions. Indirectly, the absence of follicular markers only in the areas with WNT/β-catenin pathway activation (morular structures) in this neoplasm could explain the absence of follicular differentiation in cribriform morular thyroid carcinoma. The additional study of one of the accompanying thyroid nodules (follicular nodular disease) confirmed the constitutional DICER1 variant, along with DICER1 p.(Asp1709Gly) and p.(Asp1810Val) variants.
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