We evaluated the accuracy of the ultrasound signs suggestive of complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM) in a cohort of women with histologically confirmed hydatidiform mole (HM) who presented with early pregnancy failure, including 103 CHM and 95 PHM for which ultrasound images were available. The accuracy of the differential diagnosis was significantly (p < 0.001) greater during secondary examination of ultrasound images compared with the original primary ultrasound examination. The interobserver agreement analysis indicated only a fair to moderate agreement between the two examinations (kappa value 0.41; 95% CI 0.29–0.53). Most HM present as early pregnancy failure and identification of early ultrasound signs can improve the differential diagnosis between CHM and PHM

Jauniaux, E

Johns, J

Jurkovic, D

Memtsa, M

Ross, JA

Sebire, NJ

English

UCL Discovery

 1 Ultrasound diagnosis of complete and partial 1 hydatidiform moles in early pregnancy 2 failure: an inter-observer study 3  4  5 Eric Jauniaux1, Maria Memtsa1, Jemma Johns2, Jackie A Ross2, 6 Neil J Sebire3, Davor Jurkovic1 7  8 1EGA Institute for Women’s Health, Faculty of Population Health Sciences, 9 University College London (UCL), London, UK. 10  11 2Early Pregnancy and Gynaecology Assessment Unit, Kings College Hospital, 12 London, UK. 13  14 3UCL Great Ormond Street Institute of Child Health and NIHR GOSH BRC, 15 London, UK. 16  17  18 No funding was obtained for this project. 19  20 The authors have no conflict of interest to declare. 21  22  23 Word count: 1009 24  25  26 Correspondence to: Professor Eric Jauniaux,  27 EGA Institute for Women’s Health, University College London,  28 86-96 Chenies Mews, 29 London WC1E 6HX, UK. 30 Telephone numbers: +44/207/3908113   31 Fax: +44/207/3908115 32 E-mail: e.jauniaux@ucl.ac.uk 33  34  35 Key Words: Hydatidiform mole; Complete mole; Partial mole; Ultrasound 36 imaging; First trimester; Miscarriage. 37  38  39  2 Abstract  40 We retrospectively evaluated the accuracy of the ultrasound signs at the initial 41 examination suggestive of complete hydatidiform mole (CHM) and partial 42 hydatidiform mole (PHM) in a cohort of women with histologically confirmed 43 hydatidiform mole (HM) who presented with early pregnancy failure, including 44 103 CHM and 95 PHM for which ultrasound images were available. The 45 accuracy of the differential diagnosis was significantly (p<0.001) greater during 46 secondary examination compared with the original primary ultrasound 47 examination. The interobserver agreement analysis indicated only a fair to 48 moderate agreement between the two examinations (kappa value 0.41; 95% CI 49 0.29-0.53). Most HM present as early pregnancy failure and identification of early 50 ultrasound signs at the first scan improve the diagnosis of CHM but around half 51 of PHM remains undiagnosed by ultrasound.  52 53  3 Introduction 54 Hydatidiform moles (HMs) are defined histologically by trophoblast hyperplasia 55 which may lead to the development of gestational trophoblastic neoplasia (GTN), 56 often within months after the evacuation of the molar tissue [1,2]. Microscopically, 57 complete hydatidiform moles (CHM) are characterised by generalised 58 dysmorphism, hydrops of the villous mesenchyme and absence of a fetus [3]. In 59 partial hydatidiform moles (PHM), there is fetal development and the villous 60 dysmorphic changes are focal [3]. With advances in ultrasound imaging, the 61 diagnosis of HMs has shifted from the second to the first trimester of pregnancy 62 [4-10]. Villous hydrops in HM is a progressive phenomenon and molar changes 63 may not be visible until the end of the first trimester, in particular in PHMs where 64 the molar changes are focal. 65 The vast majority of HMs miscarry in the first trimester of pregnancy and 66 the combined incidence of CHM and PHM in early pregnancy failure ranges 67 between 1 per 19 cases of clinical miscarriage [9] and 1 per 41 early pregnancy 68 losses examined histologically [11]. The risk of post-molar GTN is not affected by 69 the gestational age at diagnosis or evacuation [12] but women with CHM have a 70 15-20% risk of GTN compared to 0.5-1% for PHM [1,2].  71 Women presenting with early pregnancy failure may not be diagnosed 72 with HM if they opt for a conservative or medical management or if there is 73 insufficient villous tissue available for histopathological examination and thus will 74 not benefit from follow-up. Thus, the accuracy of the initial ultrasound 75 examination in these cases can have an impact on the management of women 76  4 with HM. In early pregnancy (4-5 weeks of gestation), CHM may appear as a 77 morphologically normal gestational sac containing a chorionic cavity and 78 sometimes a secondary yolk sac [13]. At around 6-7 weeks, the molar tissue 79 often appears as a heterogeneous, mainly dense but often polypoid mass [13-80 16], before developing into typical generalised hydatidiform mole in the following 81 weeks [13]. In PHM, the first ultrasound sign is often placental enlargement with 82 an abnormally developing fetus and the hydropic changes of some villi are often 83 not visible before 10 weeks of gestation. The purpose of the present study was to 84 evaluate the role of these early ultrasound features in the differential diagnosis 85 between CHM and PHM in women presenting with early pregnancy failure. 86  87 Methods 88 The study group included 198 patients presenting with a missed or incomplete 89 miscarriage at < 13 weeks of gestation at the Early Pregnancy Assessment Unit 90 (EPAU) at University College London (UCLH) or King’s College Hospital (KCH), 91 diagnosed histologically (Charing Cross Hospital (www.hmole-chorio.org.uk), 92 Imperial College, London) with HM following surgical evacuation, between March 93 2003 and December 2017. Only cases with ultrasound images available for 94 retrospective review were included in this study. All ultrasound images were 95 anonymised for the analysis and reviewed using previously described diagnostic 96 criteria [9,10,13].The protocol and a waiver of consent were granted a favourable 97 opinion by the NHS Health Research Authority (REC 18/WM/0328).  98  5 For the retrospective (secondary) examination, the principal investigators 99 (EJ & MM) were blinded to results of the original (primary) ultrasound 100 examination and whether histopathology diagnosis was CHM or PHM. The 101 comparison was performed for the initial ultrasound examination when the patient 102 presented for care and was diagnosed with a missed or incomplete miscarriage. 103 Stata (STATA software (version 15; StataCorp, College Station, TX) was used to 104 perform the statistical analysis. Categorical variables were compared using chi-105 squared (χ2) test. The McNemar test was used to compare the percentage of 106 cases where a correct diagnosis of CHM versus PHM was made between 107 observers at the initial ultrasound examination. Interobserver variability rates 108 were based on each observer’s first ultrasound examination. Kappa statistics and 109 percentage agreement are reported according to Landis and Koch [19]. A p value 110 of <0.05 was considered significant. 111  112 Results and Discussion 113 Ultrasound images were available for review in 198 cases of HM including 103 114 CHM and 95 PHM. Ninety-two patients had more than one ultrasound 115 examinations. Table 1 compares the results of the primary and secondary 116 evaluation at the initial ultrasound examination. Significantly (p<0.001) higher 117 correct diagnoses were found during the secondary examination compared with 118 the original primary examination. The overall interobserver agreement between 119 the primary and secondary examinations was moderate for HM (Kappa 0.41; 120 95%CI 0.29;0.53), slight for CHM (Kappa 0.15, 95%CI 0.03;0.27) and fair for 121  6 PHM (kappa value 0.39, 95% CI 0.22-0.57). These suggest that the ultrasound 122 diagnosis of PHM remains difficult even when the images are reviewed by 123 experts. 124 In the vast majority of CHM, the sonolucent cystic areas corresponding to 125 hydropic molar villi and the loss of a recognisable gestational sac should be 126 identifiable from 9 weeks of gestation on ultrasound examination. In PHM, the 127 hydropic villi are in small numbers often within an enlarged placenta and are difficult 128 to differentiate from the hydropic changes associated with prolonged retention after 129 fetal demise often seen in missed miscarriages. This can explain the higher 130 accuracy of ultrasound imaging in diagnosing CHM compared to PHM in early 131 pregnancy failure at the initial ultrasound examination. The accuracy of the 132 ultrasound diagnosis is also operator dependent and the data of the present 133 study suggest that awareness of the early ultrasound signs of CHM, which we 134 previously described [13] i.e. polypoid heterogeneous hyperechogenic mass 135 (figure 1 A), should improve the detection rate of this anomaly in women 136 presenting with early pregnancy failure.  137 In conclusion, women with HM are likely to be first seen with clinical 138 symptoms and an ultrasound diagnosis of early pregnancy failure. Awareness of 139 early ultrasound signs by ultrasound operator could improve the overall 140 management for HM with predicted detection rates of up to 95% of CHM at the 141 first ultrasound examination. It is likely that around half of PHM would remain 142 undetected by ultrasound examination, necessitating routine histological 143 evaluation of the products of conception to ensure accurate diagnosis.  144 145  7  References 146 1. M.J. Seckl, N.J. Sebire, Berkowitz RS. Gestational trophoblastic disease. 147 Lancet (2010);376:717-29. 148 2. H.Y.S. Ngan, M.J. Seckl, R.S. Berkowitz, Y. Xiang, F. Golfier, P.K. 149 Sekharan, J.R. Lurain, L. Massuger. Update on the diagnosis and 150 management of gestational trophoblastic disease. Int. J. Gynaecol. 151 Obstet. (2018); 143 Suppl 2: 79-85. 152 3. E. Jauniaux. Partial moles: from postnatal to prenatal diagnosis. Placenta 153 (1999); 20: 379-88. 154 4. E. Lazarus, C.A. Hulka, B. Siewert, D. Levine. Sonographic appearance of 155 early complete molar pregnancies. J. Ultrasound. Med. (1999); 18: 589-156 593. 157 5. C.B. Benson, D.R. Genest, M.R. Bernstein, V. Soto-Wright, D.P. 158 Goldstein, R.S. Berkowitz. 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Ultrasound diagnosis of complete and partial hydatidiform moles in early pregnancy failure: An inter-observer study

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Ultrasound diagnosis of complete and partial hydatidiform moles in early pregnancy failure: An inter-observer study

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