The diagnosis of synchronous carcinomas, involving both the endometrium and ovaries, is not a rare finding in gynecologic pathology and represents a challenge with implications on tumor staging and therapeutic decision-making. A mono-institutional series of 11 metastatic and 6 paired synchronous endometrial and ovarian carcinomas were reviewed by 2 expert pathologists based on previously published histopathologic criteria. The series was investigated for DNA mismatch repair proteins, p53, and POLE status and was subject to DNA-based next-generation sequencing targeting 67 cancer-related genes. Out of 17 pairs, 16 featured the same histotype (10 endometrioid, 4 serous high-grade, and 2 clear cells). By using WHO 2020 criteria, 11 couples of tumors were confirmed as metastatic and 6 couples were confirmed as independent. Based on next-generation sequencing analysis, 16 of 17 cases (11 metastatic and 5 independent) of our series showed evidence of a clonal relationship between endometrial and ovarian carcinomas. In metastatic cases, the adverse outcome was associated with nonendometrioid/high-grade endometrioid histotype and with the p53-abnormal molecular subtype. Four cases originally fulfilling clinicopathological criteria of independent endometrial and ovarian carcinomas were clonally related, low-grade endometrioid histotype and POLE-mut, mismatch repair deficient, and no specific molecular profile molecular subtypes; no adverse event was recorded in this group. In summary, the molecular characterization of synchronous gynecologic carcinomas confirms their clonal origin in most cases. However, the results of our study point out that the clinical behavior of these tumors seems to be determined by the presence of high-risk WHO 2020 histologic criteria and molecular features (i.e. p53-abnormal), rather than the monoclonal origin.

中文翻译：

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同步子宫内膜癌和卵巢癌：病理学和分子分析强调病变的单克隆起源。

涉及子宫内膜和卵巢的同步癌的诊断在妇科病理学中并不罕见，并且对肿瘤分期和治疗决策具有影响。2 位病理学家根据先前发表的组织病理学标准对 11 例转移性子宫内膜癌和 6 例同步子宫内膜癌和卵巢癌的单一机构系列进行了审查。该系列研究了 DNA 错配修复蛋白、p53 和 POLE 状态，并针对 67 个癌症相关基因进行了基于 DNA 的下一代测序。在 17 对中，16 对具有相同的组织型（10 个子宫内膜样细胞、4 个浆液性高级细胞和 2 个透明细胞）。根据WHO 2020标准，11对肿瘤被确认为转移性肿瘤，6对被确认为独立肿瘤。根据下一代测序分析，我们系列的 17 例病例中的 16 例（11 例为转移性病例，5 例为独立病例）显示出子宫内膜癌和卵巢癌之间存在克隆关系的证据。在转移性病例中，不良结果与非子宫内膜样/高级别子宫内膜样组织型和 p53 异常分子亚型相关。4例原本符合独立子宫内膜癌和卵巢癌临床病理标准的病例为克隆相关、低级别子宫内膜样组织型和POLE突变、错配修复缺陷、无特定分子谱分子亚型；该组中没有记录到不良事件。总之，同步性妇科癌的分子特征在大多数情况下证实了其克隆起源。然而，我们的研究结果指出，这些肿瘤的临床行为似乎是由高危WHO 2020组织学标准和分子特征（即p53异常）的存在决定的，而不是由单克隆起源决定的。