Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Division of Head and Neck Pathology and Cytopathology, Department of Pathology and Laboratory Medicine, Emory University Hospital Midtown, 550 Peachtree St, Atlanta, GA, 30309, USA.
Virchows Arch. 2023 Mar;482(3):479-491. doi: 10.1007/s00428-022-03422-4. Epub 2022 Nov 8.
Poorly differentiated thyroid carcinoma (PDTC), defined by Turin criteria, comprises a subset of high-grade follicular-derived thyroid carcinomas with intermediate prognosis. While differentiated oncocytic thyroid carcinomas demonstrate clinicopathologic and genetic differences compared to their non-oncocytic counterparts, similar data is limited in oncocytic (Hurthle) PDTCs (OPDTCs). Here, we assessed the impact of various oncocytic cut-offs in PDTCs on clinical, histologic and survival parameters.Our bi-institutional cohort comprised 210 primary PDTCs with available slides reviewed by at least one pathologist. Histologic features, including oncocytic fraction, were recorded. Clinicopathologic data were obtained, including overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), locoregional recurrence free survival (LRRFS), and distant metastasis-free survival (DMFS). Radioactive iodine avidity data was available for 125 PDTCs based on postoperative whole-body scanning.Within our cohort, 39.0% PDTCs had any oncocytic component with 24.8% meeting the 75% World Health Organization (WHO) oncocytic definition. Any oncocytic component and > 25% oncocytic cut-off correlated with decreased DSS and LRRFS, respectively, compared to non-oncocytic PDTCs (NOPDTCs) on univariate and multivariate analysis. The 100% oncocytic cut-off was significant for DSS on univariate analysis but a non-significant trend on multivariate analysis. Any oncocytic cut-off (100%, > 75%, > 50%, > 25%, or > 0%) conferred higher radioactive iodine (RAI)-refractoriness to OPDTCs compared to NOPDTCs. NF1 and PTEN alterations were enriched in OPDTCs (40% vs. 0%, and 60% vs 8%, respectively), whereas NRAS mutations were frequent in NOPDTCs (47% vs. 7%).Among PDTCs, the presence of oncocytes led to downward trend in all outcome parameters, especially for DSS and LRRFS. OPDTCs were enriched in NF1 and PTEN mutations. Consistently, all oncocytic cut-offs were associated with RAI-refractoriness. Accordingly, additional studies are needed to reassess the current 75% cut-off used to define oncocytic thyroid lesions.
未分化甲状腺癌 (PDTC) 根据都灵标准定义，由具有中间预后的高级滤泡源性甲状腺癌组成。虽然与非嗜酸性细胞相比，分化型嗜酸细胞性甲状腺癌在临床病理和遗传上存在差异，但在嗜酸细胞性 (Hurthle) PDTC (OPDTC) 中类似的数据有限。在这里，我们评估了 PDTC 中各种嗜酸性细胞截止值对临床、组织学和生存参数的影响。我们的双机构队列包括 210 例原发性 PDTC，至少有一位病理学家对其切片进行了审查。记录了组织学特征，包括嗜酸性细胞分数。获得了临床病理数据，包括总生存期 (OS)、无病生存期 (DFS)、疾病特异性生存期 (DSS)、局部区域无复发生存期 (LRRFS) 和远处转移无复发生存期 (DMFS)。根据术后全身扫描，125 例 PDTC 可获得放射性碘摄取数据。在我们的队列中，39.0%的 PDTC 有任何嗜酸性成分，24.8%符合世界卫生组织 (WHO) 75%的嗜酸性定义。任何嗜酸性成分和>25%的嗜酸性细胞截止值与非嗜酸性 PDTC (NOPDTC) 相比，在单变量和多变量分析中分别与 DSS 和 LRRFS 降低相关。在单变量分析中，100%的嗜酸性细胞截止值对 DSS 有意义，但在多变量分析中无显著趋势。与 NOPDTC 相比，任何嗜酸性细胞截止值 (100%、>75%、>50%、>25%或>0%) 均使 OPDTC 对放射性碘 (RAI) 的反应性降低。NF1 和 PTEN 改变在 OPDTC 中丰富 (40%对 0%，60%对 8%)，而 NOPDTC 中 NRAS 突变频繁 (47%对 7%)。在 PDTC 中，嗜酸性细胞的存在导致所有结局参数呈下降趋势，尤其是 DSS 和 LRRFS。OPDTC 中富含 NF1 和 PTEN 突变。一致地，所有嗜酸性细胞截止值均与 RAI 反应性相关。因此，需要进一步的研究来重新评估目前用于定义嗜酸性甲状腺病变的 75%截止值。
