Savage Johanna, Adams Emily, Veras Emanuela, Murphy Kathleen M, Ronnett Brigitte M
Departments of *Pathology ‡Gynecology & Obstetrics, The Johns Hopkins Medical Institutions, Baltimore, MD †ProPath, Dallas, TX.
Am J Surg Pathol. 2017 Dec;41(12):1593-1606. doi: 10.1097/PAS.0000000000000937.
Choriocarcinoma is an uncommon malignant neoplasm, which can be either gestational or nongestational in origin. Distinction of these subtypes has prognostic and therapeutic implications. Twenty-two tumors were genotyped using polymerase chain reaction amplification of 15 short tandem repeat loci and the amelogenin locus (XY determination). DNA patterns from tumor and maternal tissue, as well as villous tissue from any available prior or concurrent gestation, were compared, to determine gestational versus nongestational nature (containing vs. lacking a paternal chromosome complement, respectively) and the relationship between the tumor and any prior or concurrent gestation. Nineteen tumors were gestational. Of these, 14 were purely androgenetic/homozygous XX: 6 uterine tumors with a concurrent or prior genetically related complete hydatidiform mole (CHM), 4 uterine tumors without an accompanying villous component, 1 uterine cornual tumor separate from a genetically distinct second trimester intrauterine placenta, 1 ectopic ovarian tumor separate from a genetically distinct third trimester intrauterine placenta, and 2 ectopic fallopian tube tumors. Five gestational tumors were biparental: 3 (2 XX, 1 XY) intraplacental choriocarcinomas genetically related to the placenta and 2 uterine tumors without accompanying placental tissue after term deliveries (1 XX 4 weeks postpartum and 1 XYY with allelic imbalances 1 year postpartum; prior placentas not available for analysis). Three tumors were nongestational: all XX with allelic imbalances; 2 ovarian, 1 pelvic. Gestational choriocarcinoma can be androgenetic or biparental. Most are androgenetic/homozygous XX, often associated with a genetically related concurrent or prior CHM, and thus of molar-associated type. These findings support that homozygous XX CHMs are associated with some risk of significant gestational trophoblastic disease. Intraplacental choriocarcinomas are biparental and genetically related to the placenta. Biparental choriocarcinoma detected in a postpartum uterine sample is consistent with undetected intraplacental choriocarcinoma. Eutopic or ectopic androgenetic choriocarcinoma separate from a concurrent intrauterine placenta is not derived from intraplacental tumor and is consistent with either a form of dispermic twin gestation (molar-type choriocarcinoma and coexistent nonmolar fetus) or origin from an antecedent molar pregnancy. While fallopian tube tumors are usually gestational, tumors in other sites (ovary, pelvis) can be nongestational and should not be assumed to be metastatic from a regressed or occult intrauterine or intraplacental gestational tumor.
绒毛膜癌是一种罕见的恶性肿瘤，其起源可为妊娠性或非妊娠性。区分这些亚型具有预后和治疗意义。使用聚合酶链反应扩增15个短串联重复序列位点和牙釉蛋白位点（XY性别鉴定）对22个肿瘤进行基因分型。比较肿瘤组织、母体组织以及任何既往或同期妊娠的绒毛组织的DNA图谱，以确定其妊娠性与非妊娠性本质（分别为含有父系染色体互补或缺乏父系染色体互补）以及肿瘤与任何既往或同期妊娠之间的关系。19个肿瘤为妊娠性。其中，14个为纯雄激素性/纯合XX型：6个子宫肿瘤伴有同期或既往基因相关的完全性葡萄胎（CHM），4个子宫肿瘤无绒毛成分，1个子宫角部肿瘤与基因不同的孕中期宫内胎盘分离，1个异位卵巢肿瘤与基因不同的孕晚期宫内胎盘分离，2个异位输卵管肿瘤。5个妊娠性肿瘤为双亲性：3个（2个XX型，1个XY型）胎盘内绒毛膜癌与胎盘基因相关，2个足月分娩后无胎盘组织的子宫肿瘤（1个产后4周的XX型和1个产后1年等位基因失衡的XYY型；既往胎盘无法进行分析）。3个肿瘤为非妊娠性：均为等位基因失衡的XX型；2个卵巢肿瘤，1个盆腔肿瘤。妊娠性绒毛膜癌可为雄激素性或双亲性。大多数为雄激素性/纯合XX型，常与基因相关的同期或既往CHM相关，因此属于葡萄胎相关类型。这些发现支持纯合XX型CHM与严重妊娠滋养细胞疾病的某些风险相关。胎盘内绒毛膜癌为双亲性且与胎盘基因相关。产后子宫样本中检测到的双亲性绒毛膜癌与未检测到的胎盘内绒毛膜癌一致。与同期宫内胎盘分离的原位或异位雄激素性绒毛膜癌并非源自胎盘内肿瘤，符合双精双胎妊娠的一种形式（葡萄胎型绒毛膜癌和并存的非葡萄胎胎儿）或源自先前的葡萄胎妊娠。虽然输卵管肿瘤通常为妊娠性，但其他部位（卵巢、盆腔）的肿瘤可为非妊娠性，不应假定为来自退化或隐匿的宫内或胎盘内妊娠性肿瘤的转移瘤。
