Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Department of Pathology, University of Wisconsin, Madison, WI, USA.
Mod Pathol. 2019 Jul;32(8):1180-1188. doi: 10.1038/s41379-019-0266-0. Epub 2019 Apr 5.
Uniparental disomy is an abnormal genetic condition in which both homologous chromosomes or part of the chromosome are inherited from one parent and the other parent's homologous chromosome is lost. We report three cases of gestations with paternal uniparental isodisomy at tyrosine hydroxylase or TH01 locus on chromosome 11p15.4 identified by DNA genotyping. The patients' age ranged from 32 to 35 years and all patients presented with missed abortion during the first trimester. Abnormal chorionic villi were seen in all cases with histomorphological and/or p57 immunohistochemical features simulating either partial or complete mole. While two patients had an uneventful clinical course, one patient presented with clinical complications simulating persistent gestational trophoblastic disease/neoplasia that required multiagent chemotherapy with etoposide, methotrexate, actinomycin D, vincristine, and cyclophosphamide (EMA-CO). In summary, paternal uniparental isodisomy of tyrosine hydroxylase locus at chromosome 11p15.4 may result in an abnormal gestation that simulates a hydatidiform mole both clinically and histologically. The presence of abnormal trophoblastic proliferation combined with loss of p57 expression in villous cytotrophoblast and stromal cells may be associated with an aggressive clinical behavior.
单亲二体性是一种异常的遗传状况，其中两条同源染色体或染色体的一部分来自一个亲本，而另一个亲本的同源染色体丢失。我们报告了 3 例通过 DNA 基因分型鉴定的 11p15.4 染色体酪氨酸羟化酶或 TH01 位点的父源单亲二体同型性。患者年龄在 32 至 35 岁之间，所有患者均在孕早期发生流产。所有病例均可见异常绒毛，其组织形态学和/或 p57 免疫组织化学特征类似于部分或完全葡萄胎。虽然有 2 例患者临床过程无异常，但有 1 例患者出现类似于持续性妊娠滋养细胞疾病/肿瘤的临床并发症，需要多药化疗，包括依托泊苷、甲氨蝶呤、放线菌素 D、长春新碱和环磷酰胺（EMA-CO）。总之，11p15.4 染色体酪氨酸羟化酶位点的父源单亲二体性可能导致一种异常妊娠，其在临床上和组织学上均类似于葡萄胎。绒毛滋养细胞和间质细胞中存在异常的滋养细胞增殖，同时伴有 p57 表达缺失，可能与侵袭性临床行为有关。
