The diagnosis of molar pregnancy is a continuing diagnostic problem for many practicing histopathologists who are required to examine specimens of products of conception, particularly since changes in gynecological management in recent years have resulted in uterine evacuation at earlier gestations. The aim of this review is to provide practical, up-to-date, diagnostically useful information regarding the histological diagnosis of molar disease in early pregnancy. Pathophysiological issues relevant to molar pregnancies, such as genetic abnormalities, will be briefly summarized, but nonhistopathological aspects of molar disease will not be covered in detail in this review.
GoldsteinDP, BerkowitzRS. Current management of complete and partial molar pregnancy. J Reprod Med1994;39:139–146.
5.
BagshaweKD, DentJ.Hydatidiform mole in England and Wales, 1973–1983. Lancet1986;2:673–677.
6.
NewlandsES. Presentation and management of persistent gestational trophoblastic disease and gestational trophoblastic tumors in the UK. In: HancockBW, NewlandsES, BerkowitzRS, eds. Gestational Trophoblastic Disease.London: Chapman & Hall, 1997:143–156.
7.
SecklMJ, FisherRA, SalernoG, Choriocarcinoma and partial hydatidiform moles. Lancet2000;356:36–39.
8.
VassilakosP, KajiiT.Hydatidiform mole: two entities. Lancet1976;1:259.
9.
VassilakosP, RiottonG, KajiiT.Hydatidiform mole: two entities. A morphological and cytogenetic study with some clinical considerations. Am J Obstet Gynecol1977;127:167–170.
10.
SzulmanAE, SurtiU.The syndromes of hydatidiform mole. I. Cytogenetic and morphologic correlations. Am J Obstet Gynecol1978;131:665–671.
11.
KajiiT, OhamaK.Androgenetic origin of hydatidiform mole. Nature1977;268:633–634.
12.
WakeN, TakagiN, SasakiM.Androgenesis as a cause of hydatidiform mole. J Natl Cancer Inst1978;60:51–57.
13.
LawlerSD, PickthallVJ, FisherRA, PoveyS, EvansMW, SzulmanAE. Genetic studies of complete and partial hydatidiform moles. Lancet1979;2:580.
14.
JacobsPA, WilsonCM, SprenkleJA, RosensheinNB, MigeonBR. Mechanism of origin of complete hydatidiform moles. Nature1980;286:714–716.
15.
LawlerSD, PoveyS, FisherRA, PickthallVJ. Genetic studies on hydatidiform moles. II. The origin of complete moles. Ann Hum Genet1982;46:209–222.
16.
FisherRA, PoveyS, JeffreysAJ, MartinCA, PatelI, LawlerSD. Frequency of heterozygous complete hydatidiform moles, estimated by locus-specific minisatellite and Y chromosome-specific probes. Hum Genet1989;8:259–263.
17.
KovaksBW, ShahbahramiB, TastDE, CurtinJP. Molecular genetic analysis of complete hydatidiform moles. Cancer Genet Cytogenet1991;54:143–152.
18.
OhamaK, KajiiT, OkamotoE, Dispermic origin of XY hydatidiform moles. Nature1981;29:551–552.
19.
WallaceDC, SurtiU, AdamsCW, SzulmanAE. Complete moles have paternal chromosomes but maternal mitochondrial DNA. Hum Genet1982;61:145–147.
20.
EdwardsYH, JeremiahSJ, McMillanSL, PoveyS, FisherRA, LawlerSD. Complete hydatidiform moles combine maternal mitochondria with a paternal nuclear genome. Ann Hum Genet1984;48:119–127.
21.
JacobsPA, HuntPA, MatsuuraJS, WilsonCC, SzulmanAE. Complete and hydatidiform mole in Hawaii: cytogenetics, morphology and epidemiology. Br J Obstet Gynaecol1982;89:258–266.
22.
HelwaniMN, SeoudM, ZahedL, ZaatariG, KhalilA, SlimR.A familial case of recurrent hydatidiform molar pregnancies with biparental genomic contribution. Hum Genet1999;105:112–115.
23.
FisherRA, KhatoonR, ParadinasFJ, RobertsAP, NewlandsES. Repetitive complete hydatidiform mole can be biparental in origin and either male or female. Hum Re-prod2000;15:594–598.
24.
SensiA, GualandiF, PittalisMC, Mole maker phenotype: possible narrowing of the candidate region. Eur J Hum Genet2000;8:641–644.
25.
LawlerSD, FisherRA, PickthallVJ, PoveyS, EvansMW. Genetic studies on hydatidiform moles. I. The origin of partial moles. Cancer Genet Cytogenet1982;5:309–320.
26.
JacobsPA, SzulmanAE, FunkhouserJ, MatsuuraJS, WilsonCC. Human triploidy: relationship between parental origin of the additional haploid complement and development of partial hydatidiform mole. Ann Hum Genet1982;46:223–231.
27.
ZaragozaMV, SurtiU, RedlineRW, MillieE, ChakravartiA, HassoldTJ. Parental origin and phenotype of triploidy in spontaneous abortions: predominance of diandry and association with the partial hydatidiform mole. Am J Hum Genet2000;66:1807–1820.
28.
VejerslevLO, FisherRA, SurtiU, WakeN.Hydatidiform mole: cytogenetically unusual cases and their implications for the present classification. Am J Obstet Gynecol1987;157:180–184.
29.
SheppardDM, FisherRA, LawlerSD, PoveyS.Tetraploid conceptus with three paternal contributions. Hum Genet1982;62:371–374.
30.
SurtiU, SzulmanAE, WagnerK, LeppertM, O'BrienSJ. Tetraploid partial hydatidiform moles: two cases with a triple paternal contribution and a 92,XXXY karyotype. Hum Genet1986;72:15–21.
31.
ReikW, WalterJ.Genomic imprinting: parental influence on the genome. Nat Rev Genet2001;2:21–32.
32.
McFaddenDE, KwongLC, YamIY, LangloisS.Parental origin of triploidy in human fetuses: evidence for genomic imprinting. Hum Genet1993;92:465–469.
33.
ParadinasFJ. The histological diagnosis of hydatidiform moles. Curr Diagn Pathol1994;1:24–31.
34.
GenestDR. Partial hydatidiform mole: clinicopathological features, differential diagnosis, ploidy and molecular studies, and gold standards for diagnosis. Int J Gynecol Pathol2001;20:315–322.
35.
Van de KaaCA, HanselaarAGJM, HopmanAHN, DNA cytometric and interphase cytogenetic analyses of paraffin-embedded hydatidiform moles and hydropic abortions. J Pathol1993;170:229–238.
36.
FisherRA, LawlerSD, OrmerodMG, ImrieP, PoveyS.Flow cytometry used to distinguish between complete and partial hydatidiform moles. Placenta1987;8:249–256.
37.
HemmingJD, QuirkeP, WomackC, WellsM, ElstonCW. Diagnosis of molar pregnancy and persistent trophoblastic disease by flow cytometry. J Clin Pathol1987;40:615–620.
38.
LageJM, DriscollSG, YavnerDL, OlivierAP, MarkSD, WeinbergDS. Hydatidiform moles; application of flow cytometry in diagnosis. Am Clin Pathol1988;89:596–600.
39.
LeeMH, ReynisdottirI, MassagueJ.Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution. Genes Dev1995;9:639–649.
40.
ChilosiM, PiazzolaE, LestaniM, Differential expression of p57kip2, a maternally imprinted cdk inhibitor, in normal human placenta and gestational trophoblastic disease. Lab Invest1998;78:269–276.
41.
CastrillonDH, SunD, WeremowiczS, FisherRA, CrumCP, GenestDR. Discrimination of complete hydatidiform mole from its mimics by immunohistochemistry of the paternally imprinted gene product p57KIP2. Am J Surg Pathol2001;25:1225–1230.
42.
WeberJL, MayPE. Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet1989;44:388–396.
FisherRA, NewlandsES. Rapid diagnosis and classification of hydatidiform moles using the polymerase chain reaction. Am J Obstet Gynecol1993;168:563–569.
45.
LaneSA, TaylorGR, OzolsB, QuirkeP.Diagnosis of complete molar pregnancy by microsatellites in archival material. J Clin Pathol1993;46:346–348.
46.
BellKA, Van DeerlinV, AddyaK, ClevengerCV, Van DeerlinPG, LeonardDG. Molecular genetic testing from paraffin-embedded tissue distinguishes nonmolar hydropic abortion from hydatidiform mole. Mol Diagn1999;4:11–19.
47.
AmrMF, FisherRA, FoskettMA, ParadinasFJ. Triplet pregnancy with hydatidiform mole. Int J Gynecol Cancer2000;10:76–81.
48.
WeaverDT, FisherRA, NewlandsES, ParadinasFJ. Amniotic tissue in complete moles can be androgenetic. J Pathol2000;191:67–70.
49.
ReubinoffBE, LewinA, VernerM, SafranA, SchenkerJG, AbeliovichD.Intracytoplasmic sperm injection combined with preimplantation genetic diagnosis for the prevention of recurrent gestational trophoblastic disease. Hum Re-prod1997;12:805–808.
50.
EvansAC, SoperJT, HammondCB. Clinical features of molar pregnancies and gestational trophoblastic tumors. In: HancockBW, NewlandsES, BerkowitzRS, eds. Gestational Trophoblastic Disease.London: Chapman & Hall, 1997:109–125.
51.
BerkowitzRS, GoldsteinDP. Presentation and management of molar pregnancy. In: HancockBW, NewlandsES, BerkowitzRS, eds. Gestational Trophoblastic Disease.London: Chapman & Hall, 1997:127–142.
52.
ParadinasFJ. The histological diagnosis of hydatidiform moles. Curr Diagn Pathol1994;1:24–31.
53.
ParadinasFJ, BrowneP, FisherRA, FoskettM, BagshaweKD, NewlandsE.A clinical, histopathological and flow cytometric study of 149 complete moles, 146 partial moles and 107 non-molar hydropic abortions. Histopathology1996;28:101–110.
54.
BerkowitzRS, GoldsteinDP. The diagnosis of molar pregnancy by ultrasound: a continuing challenge. Ultrasound Obstet Gynecol1997;9:4–5.
55.
SebireNJ, ReesH, ParadinasFJ, SecklMJ, NewlandsES. The diagnostic implications of routine ultrasound examination in histologically confirmed early molar pregnancies. Ultrasound Obstet Gynecol2001;18:662–665.
56.
ParadinasFJ. The diagnosis and prognosis of molar pregnancy: the experience of the National Referral Centre in London. Int J Gynaecol Obstet1998;60: Suppl 1:S57–S64.
57.
FisherRA, ParadinasFJ, SoteriouBA, FoskettM, New-landsES. Diploid hydatidiform moles with fetal red blood cells in molar villi. 2—Genetics. J Pathol1997;181:189–195.
58.
SebireNJ, ReesH, ParadinasFJ, Extravillus endovascular implantation site trophoblast invasion is abnormal in complete versus partial molar pregnancies. Placenta2001;22:725–728.
59.
ParadinasFJ, FisherRA, BrowneP, NewlandsES. Diploid hydatidiform moles with fetal red blood cells in molar villi. 1—Pathology, incidence, and prognosis. J Pathol1997;181:183–188.
60.
JauniauxE, NicolaidesKH, HustinJ.Perinatal features associated with placental mesenchymal dysplasia. Placenta1997;18:701–706.
61.
ParadinasFJ, SebireNJ, FisherRA, Pseudo-partial moles; placental stem vessel hydrops and the association with Beckwith-Wiedemann syndrome and complete moles. 15 cases and a review of the literature. Histopathology2001;39:447–454.
62.
CheungANY, NganHYS, ChenWZ, The significance of the proliferating cell nuclear antigen in human trophoblastic disease: an immunohistochemical study. Histopathology1993;22:565–568.
63.
SureshUR, HaleRJ, FoxH, BuckleyCH. Use of proliferation cell nuclear antigen immunoreactivity for distinguishing hydropic abortions from partial hydatidiform moles. J Clin Pathol1993;46:48–50.
64.
OlveraM, HarrisS, AmezcuaCA, Immunohistochemical expression of cell cycle proteins E2F-1, Cdk-2, Cyclin E, p27 (kip1) and Ki-67 in normal placenta and gestational trophoblastic disease. Mod Pathol2001;14:1036–1042.
