1 Departments of Obstetrics and Gynaecology and 2 Pathology, Ioannina University Hospital, Ioannina, Greece and 3 Trophoblastic Screening and Treatment Centre, Charing Cross Hospital, London, UK
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Abstract |
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Key words: androgenetic/complete hydatidiform mole/monospermic/live birth/placental mosaicism
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Introduction |
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We present a case of a singleton pregnancy with prenatally detected diffuse placental molar change, resulting in a phenotypically normal female infant at term, which we believe represents the first well-documented case of apparent confined placental mosaicism for CM with a coexisting normal fetus.
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Case Report |
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A total of 50 ng of DNA from the patient and her partner and 1 µl DNA from each of the tissue DNA samples was amplified using pairs of fluorescently labelled primers which flank polymorphic microsatellite repeats. One pair of primers was used for each of the 22 pairs of autosomes (Reed et al., 1994). Following amplification, 5 µl of each PCR reaction product underwent electrophoresis in a 1% agarose gel to assess the yield of product. PCR products were diluted as appropriate and subsequently resolved by capillary electrophoresis using an ABI Prism 310 Genetic Analyser (Applied Biosystems Ltd, UK). Analysis and sizing of the microsatellite polymorphisms was performed using ABI Prism GeneScan software (Applied Biosystems Ltd). Where a marker was uninformative with respect to the paternal contribution to the tissue, a further marker for that chromosome was examined.
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Results |
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Discussion |
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Confined placental mosaicism occurs in ~2% of viable pregnancies as a result of mitotic non-disjunction or translocation in the progenitor cells of specific placental cell lineages (Kalousek and Vekemans, 1996). It is difficult to envisage a mechanism that would result in loss of the complete maternal chromosome complement during mitosis of one of the cells of the trophoblast lineage, suggesting that the events giving rise to mosaicism in this case may have occurred as early as the first post-zygotic division. We propose that, following normal fertilization, asynchronous mitosis of the male pronucleus gave rise to a cell containing two identical male, and one female, pronucleus. At cleavage this would result in two blastomeres, one containing a male and female pronucleus and the other a single male pronucleus. The first blastomere would have the potential to develop normally while the second, following a subsequent failure of cytokinesis, or endoreduplication of the nucleus, would result in a second, androgenetic, cell line. Since ploidy studies were not carried out, we cannot formally exclude the possibility of the androgenetic cell line in this case being haploid.
Since the fetus was normal at birth and the child continues to develop normally at 15 months, the androgenetic cell line appears to be confined to the placental tissue. The fetus develops from only a small number of embryonic progenitor cells which may all have originated in the normal cell population in this case. Alternatively, preferential partitioning of the androgenetic cells to the extraembryonic cell lineages (Thomson and Solter, 1988) may have resulted in androgenetic cells being confined to the placenta. However, the presence of androgenetic cells in some tissues in the child cannot be excluded.
The vast majority of pregnancies with an apparently normal fetus in conjunction with molar change in the placenta, and identified by ultrasound examination, represent either triploid partial mole, in which there would be no viable fetus, or dizygotic twin pregnancies in which one conceptus is a CM and the other a normal co-twin (Paradinas, 1997). Pseudomolar changes may also be present in placental mesenchymal dysplasia, a condition usually associated with an apparently normal fetus (although there is an association with BeckwithWiedemann syndrome), but with distinctive, non-molar, histopathological features (Paradinas et al., 2001
). The association of CM and live fetus in the same pregnancy is well reported but these cases represent dizygotic twin pregnancies with molar change in one conceptus (Fisher et al., 1982
; Altaras et al., 1992
; Hsu et al., 1993
; Miller et al., 1993
; Stellar et al., 1994
; Hurteau et al., 1997
; Fishman et al., 1998
; Matsui et al., 2000
). Where genetic studies have been carried out in these cases, the normal and molar placentas have been genetically distinct.
Previous publications have reported apparent singleton pregnancies with hydatidiform molar change and co-existent live fetus but these cases either show different pathological findings to the present case and/or have not provided genetic analysis of the molar tissue (Crooij et al., 1985; Feinberg et al., 1988
; Pool et al., 1989
; Hsieh et al., 1999
). In three cases where genetic studies were performed, the placenta was shown to comprise two cell lines, one diploid and one triploid (Sarno et al., 1993
; Ikeda et al., 1996
; Zhang et al., 2000
) consistent with the presence of both a normal and PM cell line. A case of CM was described as mosaic, following growth of both biparental and androgenetic cells from cultured tissue (Ford et al., 1986
). However, the biparental cell line could have arisen from the cells of an unrecognized twin pregnancy and, in any event, unlike the present case, involved two different sperm.
The present case demonstrates clear, focal, pathological changes of CM, distinct from either partial molar change or placental mesenchymal dysplasia, and genetic analysis confirms the androgenetic, monospermic DNA content of the molar tissue. To the best of our knowledge, the present case is the first reported with pathological and genetic confirmation, in which both androgenetic CM and normal fetal cell lines are present in the same placenta. The concept that CM never occurs in the presence of a normal fetus, except in dizygotic twin pregnancies, is no longer tenable since in very rare situations, such as the present case, a post-fertilization event may also result in molar change. Since, both pathologically and genetically, the CM tissue appears identical to otherwise classical CM, the implications for the current patient in terms of risk of persistent trophoblastic disease are presumably the same as for any other CM, and appropriate surveillance with serial hCG estimations is being carried out (Newlands, 1997). The pregnancy was uncomplicated by severe obstetric conditions such as pre-eclampsia or antepartum haemorrhage in this case, although an increased prevalence of such complications in twin pregnancies with coexistent CM has been reported (Matsui et al., 2000
). Pregnancy management must be determined on an empirical basis in these rare conditions and the possible increased risks of pregnancy complications should be discussed with the patient.
In summary, we have described a unique singleton pregnancy with normal fetus and placental mosaicism for androgenetic, monospermic CHM. This case illustrates a potential new mechanism for the development of diffuse molar change, mimicking PM.
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Acknowledgements |
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Notes |
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References |
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Crooij, M.J., Van Der Harten, J.J., Puyenbroek, J.I., Van Geijn, H.P. and Arts, N.F. (1985) A partial hydatidiform mole, dispersed throughout the placenta, coexisting with a normal living fetus. Case report. Br. J. Obstet. Gynaecol., 92, 104106.[ISI][Medline]
Feinberg, R.F., Lockwood, C.J., Salafia, C. and Hobbins, J.C. (1988) Sonographic diagnosis of a pregnancy with a diffuse hydatidiform mole and coexistent 46,XX fetus: a case report. Obstet. Gynecol., 72, 485488.[Abstract]
Fisher, R.A., Sheppard, D.M. and Lawler, S.D. (1982) Twin pregnancy with complete hydatidiform mole (46, XX) and fetus (46, XY): genetic origin proved by analysis of chromosome polymorphisms. Br. Med. J., 284, 12181220.[ISI][Medline]
Fishman, D.A., Padilla, L.A., Keh, P., Cohen, L., Frederiksen, M. and Lurain, J.R. (1998) Management of twin pregnancies consisting of a complete hydatidiform mole and normal fetus. Obstet. Gynecol., 51, 546550.
Ford, J.H., Brown, J.K., Lew, W.Y. and Peters, G.B. (1986) Diploid complete hydatidiform mole, mosaic for normally fertilized cells and androgenetic homozygous cells. Case report. Br. J. Obstet. Gynaecol., 93, 11811186.[ISI][Medline]
Hsieh, C., Kuo, D.M., Lo, L.M. and Hung, T.H. (1999) Delivery of a severely anaemic fetus after partial molar pregnancy: clinical and ultrasonographic findings. Hum. Reprod., 14, 11221126.
Hsu, C.C., McConnell, J., Ko, T.N. and Braude, P.R. (1993) Twin pregnancy consisting of a complete hydatidiform mole and a fetus: genetic origin determined by DNA typing. Br. J. Obstet. Gynaecol., 100, 867869.[ISI][Medline]
Hurteau, J.A., Roth, L.M., Schilder, J.M. and Sumners, J. (1997) Complete hydatidiform mole coexisting with a twin live fetus. Gynecol. Oncol., 66, 156159.[ISI][Medline]
Ikeda, Y., Jinno, Y., Masuzaki, H., Niikawa, N. and Ishimaru, T. (1996) A partial hydatidiform mole with 2N/3N mosaicism identified by molecular analysis. J. Assist. Reprod. Genet., 13,739744.
Kajii, T. and Ohama, K. (1977) Androgenetic origin of hydatidiform mole. Nature, 268, 633634.[ISI][Medline]
Kalousek, D.K. and Vekemans, M. (1996) Confined placental mosaicism. J. Med. Genet., 33, 529533.[Abstract]
Lawler, S.D., Fisher R.A., Pickthall, V.J., Povey, S. and Evans, M.W. (1982) Genetic studies on hydatidiform moles. I. The origin of partial moles. Cancer Genet. Cytogenet., 5, 309320.[ISI][Medline]
Matsui, H., Sekiya, S., Hando, T., Wake, N. and Tomoda, Y. (2000) Hydatidiform mole coexistent with a twin live fetus: a national collaborative study in Japan. Hum. Reprod., 15, 608611.
Miller, D., Jackson, R., Ehlen, T. and McMurtrie, E. (1993) Complete hydatidiform mole coexistent with a twin live fetus: clinical course of four cases with complete cytogenetic analysis. Gynecol. Oncol., 50, 119123.[ISI][Medline]
Newlands, E.S. (1997) Presentation and management of persistent gestational trophoblastic disease and gestational trophoblastic tumors in the UK. In Hancock, B.W., Newlands, E.S. and Berkowitz, R.S. (eds), Gestational Trophoblastic Disease. Chapman & Hall, London, pp. 143156.
Paradinas, F.J. (1994) The histological diagnosis of hydatidiform moles. Curr. Diagn. Pathol., 1, 2431.
Paradinas, F.J. (1997) Pathology. In Hancock, B.W., Newlands, E.S. and Berkowitz, R.S. (eds), Gestational Trophoblastic Disease. Chapman & Hall, London, pp. 4376.
Paradinas, F.J., Sebire, N.J., Fisher, R.A., Rees, H.C., Foskett, M., Seckl, M.J. and Newlands, E.S. (2001) Pseudo-partial moles: placental stem vessel hydrops and the association with BeckwithWiedemann syndrome and complete moles. Histopathology, 39, 447454.[ISI][Medline]
Pool, R., Lebethe, S.J. and Lancaster, E.J. (1989) Partial hydatidiform mole with coexistent live full-term fetus. A case report. S. Afr. Med. J., 75, 186187.[ISI][Medline]
Reed, P.W., Davies, J.L., Copeman, J.B., Bennett, S.T., Palmer, S.M., Pritchard, L.E., Gough, S.C., Kawaguchi, Y., Cordell, H.J., Balfour, K.M. et al. (1994) Chromosome-specific microsatellite sets for fluorescence-based, semi-automated genome mapping. Nature Genet., 7, 390395.[ISI][Medline]
Sarno, A.P. Jr, Moorman, A.J. and Kalousek, D.K. (1993) Partial molar pregnancy with fetal survival: an unusual example of confined placental mosaicism. Obstet. Gynecol., 82, 716719.[Abstract]
Stellar, M.A., Genest, D.R., Bernstein, M.R., Lage, J.M., Goldstein, D.P. and Berkowitz, R.S. (1994) Clinical features of multiple conception with partial or complete molar pregnancy and coexisting fetuses. J. Reprod. Med., 39, 147154.[ISI][Medline]
Thomson, J.A. and Solter, D. (1988) The developmental fate of androgenetic, parthenogenetic, and gynogenetic cells in chimeric gastrulating mouse embryos. Genes Dev., 2, 13441351.[Abstract]
Wright, D.K. and Manos, M.M. (1990) Sample preparation from paraffin-embedded tissues. In Innis, M.A., Gelfand, D.H., Sninsky, J.J. and White, T.J. (eds), PCR Protocols, A Guide to Methods and Applications, Academic Press, New York, pp. 153158.
Zhang, P., McGinniss, M..J, Sawai, S. and Benirschke, K. (2000) Diploid/triploid mosaic placenta with fetus. Towards a better understanding of partial moles. Early Hum. Dev., 60, 111.[ISI][Medline]
Submitted on April 11, 2002; accepted on May 14, 2002.