甲状腺乳头状癌（PTC）是最常见的甲状腺恶性肿瘤，其中部分亚型呈现中至高侵袭性，其精准识别对病人预后评估和个体化治疗至关重要。第五版世界卫生组织（WHO）分类强调“细胞/组织学-分子”整合诊断模式，并首次明确高危组织学亚型，包括高细胞型、鞋钉型和柱状细胞型。弥漫硬化型、实体/梁状型等虽属中危，但同样具有较高转移风险。分子学特征在不同亚型间差异显著，如弥漫硬化型常伴RET融合，高细胞型多见BRAF V600E及TERT启动子突变，鞋钉型则与TP53突变密切相关。高级别甲状腺乳头状癌以坏死和高核分裂像为特征，生物学行为接近低分化癌。规范化病理诊断需结合充分取材、免疫组化及分子检测，以避免误诊或漏诊。分子分型能进一步指导风险分层及靶向治疗选择。少见亚型PTC的诊断正逐步从单纯形态学向整合分子病理学转变，为精准医学和个体化治疗奠定基础。
Abstract
Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, and a subset of subtypes exhibits moderate to high aggressiveness; accurate recognition is pivotal for prognostic assessment and individualized management. The fifth edition of the World Health Organization (WHO) classification emphasizes an integrated histologic-molecular diagnostic paradigm and, for the first time, explicitly designates high-risk histologic subtypes, including the tall cell subtype, hobnail subtype, and columnar cell subtype. Although the diffuse sclerosing subtype and the solid/trabecular subtype are categorized as intermediate risk, they likewise carry a considerable risk of metastasis. Distinct molecular profiles characterize these subtypes: the diffuse sclerosing subtype frequently harbors RET fusions; the tall cell subtype commonly shows BRAF V600E and TERT promoter mutations; and the hobnail subtype is closely associated with TP53 mutations. High-grade PTC, defined by tumor necrosis and a high mitotic rate, demonstrates biological behavior approaching that of poorly differentiated thyroid carcinoma. Standardized pathologic diagnosis requires adequate sampling in combination with immunohistochemistry and molecular testing to minimize misdiagnosis or underdiagnosis. Molecular subtyping further informs risk stratification and selection of targeted therapies. Overall, the diagnosis of rare PTC subtypes is transitioning from morphology alone to integrated molecular pathology, thereby laying the foundation for precision medicine and individualized treatment.
关键词
甲状腺乳头状癌 /
WHO分类 /
少见亚型 /
诊断要点 /
分子特征
Key words
papillary thyroid carcinoma /
WHO classification /
rare subtypes /
diagnostic points /
molecular characteristics
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