Bynum Jennifer, Murphy Kathleen M, DeScipio Cheryl, Beierl Katie, Adams Emily, Anderson Derek, Vang Russell, Ronnett Brigitte M
Departments of Pathology (J.B., C.D., K.B., E.A., D.A., R.V., B.M.R.) Gynecology and Obstetrics (C.D., R.V., B.M.R.), The Johns Hopkins Medical Institutions, Baltimore, Maryland ProPath (K.M.M.), Dallas, Texas.
Int J Gynecol Pathol. 2016 Mar;35(2):134-41. doi: 10.1097/PGP.0000000000000232.
Complete hydatidiform moles (CHM) are purely androgenetic conceptions, with most (∼85%) arising from fertilization of an egg lacking maternal DNA by a single sperm that duplicates (homozygous/monospermic 46,XX) and a small subset arising via fertilization by 2 sperms (heterozygous/dispermic 46,XY or 46,XX). It remains controversial if heterozygous/dispermic CHMs have a significantly greater risk of persistent gestational trophoblastic disease. Analysis of zygosity of CHMs with and without invasion at presentation, including invasive CHMs with concurrent atypical trophoblastic proliferations concerning for or consistent with choriocarcinoma, has not been specifically addressed. In a prospective series of 1024 products of conception specimens subjected to immunohistochemical analysis of p57 expression and molecular genotyping with short tandem-repeat markers, 288 CHMs were diagnosed, of which 126 were genotyped, including 16 invasive CHMs. Zygosity was compared between those with and without invasion. Of the 16 study cases, 12 (75%) were homozygous/monospermic XX and 4 (25%) were heterozygous/dispermic (3 XY and 1 XX). Of the 110 genotyped noninvasive CHMs, 96 (87%) were homozygous/monospermic XX and 14 (13%) were heterozygous/dispermic (12 XY, 2 XX). Comparison of the zygosity results for the invasive CHMs (study group) with the noninvasive CHMs in the database did not demonstrate a statistically significant difference (P=0.24, Fisher exact test). In addition, of the 3 cases associated with metastatic gestational trophoblastic disease (pulmonary nodules) at presentation, 2 were homozygous/monospermic XX, indicating that this form is not without risk of significant gestational trophoblastic disease. Thus, the current study has demonstrated a higher frequency of heterozygous/dispermic CHMs among invasive cases compared with those lacking invasion, but does not support the use of zygosity data for risk assessment of CHMs. A persistent, unresolved diagnostic challenge identified in some invasive CHMs is interpretation of accompanying florid atypical trophoblastic proliferations which raise concern for choriocarcinoma. Future studies should address the need for reproducible diagnostic criteria and molecular biomarkers for distinguishing florid hyperplastic from malignant neoplastic trophoblastic proliferations.
完全性葡萄胎（CHM）是纯雄核发育的概念，大多数（约85%）源于单个精子使缺乏母源DNA的卵子受精，该精子进行复制（纯合子/单精子受精46,XX），一小部分通过两个精子受精产生（杂合子/双精子受精46,XY或46,XX）。杂合子/双精子受精的完全性葡萄胎是否有显著更高的持续性妊娠滋养细胞疾病风险仍存在争议。对于有侵袭和无侵袭表现的完全性葡萄胎的合子性分析，包括伴有可疑或符合绒毛膜癌的非典型滋养细胞增生的侵袭性完全性葡萄胎，尚未得到专门研究。在一项对1024例妊娠产物标本进行p57表达免疫组化分析和短串联重复序列标记分子基因分型的前瞻性研究中，诊断出288例完全性葡萄胎，其中126例进行了基因分型，包括16例侵袭性完全性葡萄胎。比较了有侵袭和无侵袭者的合子性。在16例研究病例中，12例（75%）为纯合子/单精子受精XX型，4例（25%）为杂合子/双精子受精型（3例为46,XY，1例为46,XX）。在110例基因分型的非侵袭性完全性葡萄胎中，96例（87%）为纯合子/单精子受精XX型，14例（13%）为杂合子/双精子受精型（12例为46,XY，2例为46,XX）。将侵袭性完全性葡萄胎（研究组）与数据库中的非侵袭性完全性葡萄胎的合子性结果进行比较，未显示出统计学上的显著差异（P = 0.24，Fisher精确检验）。此外，在3例初诊时伴有转移性妊娠滋养细胞疾病（肺结节）的病例中，2例为纯合子/单精子受精XX型，这表明这种类型并非没有发生严重妊娠滋养细胞疾病的风险。因此，目前的研究表明，与无侵袭的病例相比，侵袭性病例中杂合子/双精子受精的完全性葡萄胎频率更高，但不支持使用合子性数据进行完全性葡萄胎的风险评估。在一些侵袭性完全性葡萄胎中发现的一个持续未解决的诊断挑战是对伴随的明显非典型滋养细胞增生的解读，这些增生引发了对绒毛膜癌的担忧。未来的研究应解决区分明显增生性与恶性肿瘤性滋养细胞增生所需的可重复诊断标准和分子生物标志物的问题。
