Over-diagnosis of hydatidiform mole in early tubal ectopic pregnancy J L Burton,E A Lidbury, 1 A M Gillespie, 1 J A Tidy, 2 O Smith, 3 J Lawry, 3 B W Hancock 1 & M Wells Section of Oncology and Pathology, Division of Genomic Medicine, University of Shef®eld Medical School, 1 YCR Department of Clinical Oncology, Weston Park Hospital, 2 Department of Obstetrics and Gynaecology, Northern General Hospital, 3 YCR Institute for Cancer Studies, Section of Oncology and Pathology, Division of Genomic Medicine, University of Shef®eld Medical School, Shef®eld, UK Date of submission 16 June 2000 Accepted for publication 10 November 2000 Burton J L,Lidbury E A,Gillespie A M, Tidy J A, Smith O, Lawry J, Hancock B W & Wells M (2001) Histopathology 38, 409±417 Over-diagnosis of hydatidiform mole in early tubal ectopic pregnancy Aims: Tubal ectopichydatidiform molesare rare lesions,and only 40 cases have been reported in the world literature. We investigated the apparently high incidenceof tubal ectopichydatidiform molesin women referredfor treatmentto a Supraregional Trophoblastic Tumour Screening and Treatment Cen- tre between 1986 and 1996. Methods and results: Of 4261 women referred during the study period,25 (0.6%) had a suspected tubal ectopic hydatidiform mole and paraf®n-embedded tis- sue was available in 20 (80%) of these. Each case was reviewed by two pathologists and DNA ¯ow cytometric analysis was undertaken when the histological diag- nosis was initially deemed equivocal or suggestive of hydatidiform mole. On review, 17 cases (85%) showed no evidenceof hydatidiform mole(circumferential trophoblasticproliferation,hydrops,scallopedvilli, and stromalkaryorrhexis). Of these,11 cases (65%) showed features of early placentation and six (35%) showed hydropic abortion. DNA ¯ow cytometry was performed in 14 (82%) of these cases and revealed a diploid population in each case. Three cases of molar pregnancy (15%) were identi®ed. Each ofthese cases had the histologicalfeaturesof an early complete hydatidiform mole. Suf®cient tissue was available for DNA ¯ow cytometric analysis in two of these cases and con®rmed the presence of diploidy in each. Conclusions: Our results show that tubal ectopic hyda- tidiform mole is a rare entity and demonstrate that it is over-diagnosed. Polar trophoblastic proliferation and hydropic villi are features of early placentation and of hydropic abortion. Sheetsofextravilloustrophoblast may be particularly prominent in tubal ectopic gesta- tion. In the absence ofcircumferential trophoblastic proliferation combined with hydropic change a diagno- sis of gestational trophoblastic disease should be avoided. Keywords: hydatidiform mole, ectopic pregnancy, ¯ow cytometry Introduction Hydatidiform moles are abnormal gestations charac- terized by the presence of hydropic change affecting someor all of the placentalvilli accompanied by markedcircumferential proliferation oftrophoblast. Molar pregnancies should be differentiated from non- molar hydropic abortions. The former achieve clinical importance because of their potential to give rise to persistent gestational trophoblastic disease, choriocar- cinoma, and placental site trophoblastic tumour. 1,2 Hydatidiform moles arise as a result of the fertiliza- tion ofan abnormal ovum.Complete moles (CM) are most often 46,XX with a genome that is entirely paternalin origin. Jacobset al. 3 have demonstrated that CM most often arises from the fertilization of an `empty' ovum by a haploid spermatozoon that subse- quently duplicates without cytogenesis to restore the diploid number. Occasionalcasesoccur when an Address for correspondence: Dr Julian L Burton, Academic Unit of Pathology, University of Shef®eld Medical School, Beech Hill Road, Shef®eld S10 2RX, UK. e-mail: j.l.burton@shef.ac.uk Ó 2001 Blackwell Science Limited. Histopathology 2001, 38, 409±417