The American Journal of Surgical Pathology ( IF 5.6 ) Pub Date : 2022-09-01 , DOI: 10.1097/pas.0000000000001893 Deyin Xing 1, 2, 3 , Emily Adams 1 , Ying S Zou 1 , Laura Morsberger 1 , Lori R Scanga 4 , Faye F Gao 5 , Norman Barker 1 , Russell Vang 1, 2 , Brigitte M Ronnett 1, 2
Complete hydatidiform moles (CHMs) and partial hydatidiform moles (PHMs) are abnormal gestations characterized by vesicular chorionic villi accompanied by variable trophoblastic hyperplasia, with or without embryonic development. CHMs are purely androgenetic (only paternal [P] chromosome complements), mostly homozygous/monospermic (~85%) but occasionally heterozygous/dispermic, whereas PHMs are overwhelmingly diandric triploid (2 paternal [P] and 1 maternal [M] chromosome complements) and heterozygous/dispermic (>95%). The presence of a fetus in a molar pregnancy usually indicates a PHM rather than a CHM; however, CHMs and PHMs rarely can be associated with a viable fetus or a nonmolar abortus in twin pregnancies and rare multiple gestation molar pregnancies have been reported. A “one-oocyte-model,” with diploidization of dispermic triploid zygotes, has been proposed for twin CHM with coexisting fetus, and a “two-oocyte-model” has been proposed for twin PHM with coexisting fetus. Among 2447 products of conception specimens, we identified 21 cases of twin/multiple gestations with a molar component, including 20 CHMs (17 twins, 2 triplets, 1 quintuplet) and 1 PHM (twin). P57 immunohistochemistry was performed on all; DNA genotyping of molar and nonmolar components was performed on 9 twin CHMs, 1 triplet CHM, 1 quintuplet CHM, and 1 twin PHM. All CHM components were p57-negative and those genotyped were purely androgenetic. Twin CHMs had genotypes of P1M1+P2P2 in 5, P1M1+P1P1 in 1, and P1M1+P2P3 in 1, consistent with involvement of 1 oocyte and from 1 to 3 sperm—most commonly a homozygous CHM but involving 2 sperm in the whole conception—and compatible with a “one-oocyte-model.” The triplet CHM was P1M1+P1P1+P2M2 and the quintuplet CHM was P1M1+P2M2+P2M2+P3M3+P4P4, consistent with involvement of 2 sperm and at least 2 oocytes for the triplet and 4 sperm and at least 3 oocytes for the quintuplet. The twin PHM had a P1M1+P2P3M2 genotype, consistent with involvement of 2 oocytes and 3 sperm. p57 immunohistochemistry is highly reliable for diagnosis of CHMs in twin/multiple gestations. Refined diagnosis of molar twin/multiple gestations is best accomplished by correlating morphology, p57 immunohistochemistry, and molecular genotyping, with the latter clarifying zygosity/parental chromosome complement contributions to these conceptions.
中文翻译:
双胎/多胎葡萄胎:21例临床病理分析,重点关注分子基因分型和父母贡献
完全性葡萄胎(CHM)和部分性葡萄胎(PHM)是异常妊娠,其特征是水泡绒毛膜绒毛伴有不同程度的滋养细胞增生,有或没有胚胎发育。CHM 是纯粹的雄激素遗传(仅父本 [P] 染色体补体),大多数是纯合/单精(~85%),但偶尔是杂合/分散,而 PHM 绝大多数是二雄三倍体(2 个父本 [P] 和 1 个母本 [M] 染色体补体)和杂合/分散 (>95%)。葡萄胎妊娠中胎儿的存在通常表明 PHM 而不是 CHM;然而,CHM 和 PHM 很少与双胎妊娠中可存活的胎儿或非葡萄胎流产相关,并且有罕见的多胎葡萄胎妊娠的报道。“单卵母细胞模型,”与分散三倍体受精卵的二倍化,已被提出用于具有共存胎儿的双胞胎 CHM,并且已针对具有共存胎儿的双胞胎 PHM 提出了“双卵母细胞模型”。在2447件受孕标本中,我们鉴定出21例具有磨牙成分的双胞胎/多胞胎妊娠,其中CHM 20例(双胞胎17例、三胞胎2例、五胞胎1例)和PHM(双胞胎)1例。对所有人进行P57 免疫组织化学分析;对 9 个双胞胎 CHM、1 个三联体 CHM、1 个五联体 CHM 和 1 个双胞胎 PHM 进行了摩尔和非摩尔成分的 DNA 基因分型。所有 CHM 成分均为 p57 阴性,且基因分型纯属雄激素遗传。双生 CHM 的基因型为 P1M1+P2P2,有 5 例,P1M1+P1P1,有 1 例,P1M1+P2P3,有 1 例,与涉及 1 个卵母细胞和 1 至 3 个精子一致,最常见的是纯合子 CHM,但在整个受孕过程中涉及 2 个精子——并且与“单卵母细胞模型”兼容。三联体 CHM 为 P1M1+P1P1+P2M2,五联体 CHM 为 P1M1+P2M2+P2M2+P3M3+P4P4,与三联体涉及 2 个精子和至少 2 个卵母细胞以及五联体涉及 4 个精子和至少 3 个卵母细胞一致。这对双胞胎 PHM 具有 P1M1+P2P3M2 基因型,与 2 个卵母细胞和 3 个精子的参与一致。p57 免疫组织化学对于诊断双胎或多胎妊娠中的 CHM 非常可靠。磨牙双胞胎/多胎妊娠的精细诊断最好通过关联形态学、p57 免疫组织化学和分子基因分型来完成,后者阐明接合性/亲代染色体补体对这些概念的贡献。