尽管上皮样滋养层肿瘤（ETT）主要起源于子宫，但越来越多的病例在子宫外发生，起源于异位妊娠或表现为转移性肿瘤，导致了与有滋养层分化的体细胞癌的主要鉴别诊断。对妊娠滋养层肿瘤与其体细胞癌模拟的精确区分对患者的管理和预后至关重要。我们总结了四例在子宫外发生的具有挑战性上皮样恶性肿瘤的临床病理和分子特征，其中ETT是主要的鉴别诊断。所有四个肿瘤均表现出组织学和免疫组化特征在体细胞癌和ETT之间重叠，同时伴有临床和影像学检查结果不确定的情况。其中两例证实了血清β-hCG水平升高。在所有病例中进行了短串联重复（STR）基因分型，且结果均有信息。肿瘤组织中存在独特的父系等位基因型模式，确认了ETT的诊断，这两例最初考虑是体细胞癌或妊娠滋养层肿瘤的疑似病例。其他两例显示与患者配对正常组织的遗传概况相匹配（最初均被视为ETT），确认了它们的体细胞来源，其中包括一例转移性三阴性乳腺癌和一例原发性肺癌。在组织学和免疫组化水平上，将在子宫外的ETT与其体细胞癌模拟的精确区分是困难的。STR基因分型提供了一个可靠的辅助工具，可以准确区分ETT和带有滋养层分化的体细胞癌。© 2023 John Wiley & Sons Ltd.

While epithelioid trophoblastic tumour (ETT) primarily arises from the uterus, cases have been increasingly documented at extrauterine sites, originating from an ectopic gestation or presenting as a metastatic tumour, leading to the major differential diagnosis of somatic carcinoma with trophoblastic differentiation. The precise separation of a gestational trophoblastic tumour from its somatic carcinoma mimics is highly relevant and crucial for patient management and prognosis.We summarise the clinicopathological and molecular features of four challenging epithelioid malignancies presenting at extrauterine sites, with ETT as the main differential diagnosis. All four tumours demonstrated histological and immunohistochemical features overlapping between a somatic carcinoma and an ETT, combined with inconclusive clinical and imaging findings. Serum beta-hCG elevation was documented in two cases. Short tandem repeat (STR) genotyping was performed and was informative in all cases. The presence of a unique paternal allelic pattern in the tumour tissue confirmed the diagnosis of ETT in two cases with an initial consideration of either somatic carcinoma or suspicion of a gestational trophoblastic tumour. The presence of matching genetic profile with the patient's paired normal tissue was seen in two other cases (both initially considered as ETT), confirming their somatic origin, including one metastatic triple-negative breast carcinoma and one primary lung carcinoma.Diagnostic separation of ETT at an extrauterine site from its somatic carcinoma mimics can be difficult at the histological and immunohistochemical levels. STR genotyping offers a robust ancillary tool that precisely separates ETT from somatic carcinomas with trophoblastic differentiation.© 2023 John Wiley & Sons Ltd.