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Case report

Two cases of pseudo―partial mole of placenta

Department of Pathology, Pathology Center ; Pathologist１），Department of Genetic diagnosis（Chu―etsugenetic diagnosis study group）；Clinical technologist２）

Toshihiko Ikarashi１），Hidehiro Hasegawa２）

Background : Though pseudo―partial mole was not agestational trophoblastic disease, it was frequently treatedas partial mole. In a meaning to avoid a useless treat-ment, the spread and the establishment of diagnosis of thisdisease were recommended. Cases : Two cases withpseudo―partial mole of placenta in mid―and late trimesterswere reported. Each placenta was very heavy in spite ofappropriate―for―gestational―aged female babies. Placentalstem villous hydrops was pathognomonic and each pla-centa revealed diploid pattern of４６，XX by fluorescencein situ hybridization（FISH）．Our cases were diagnosedas pseudo―partial mole because of a genetically diploidpattern, a pregnancy sustained until mid―trimester, and adefect of chorionic epithelial proliferation. Conclusion :FISH was very effective method to confirm pseudo―par-tial mole as to omit an unnecessary treatment against ges-tational trophoblastic disease.

Key words : pseudo―partial mole, placental stem villoushydrops, mesenchymal dysplasia of placenta, chorioan-gioma, diploid, fluorescence in situ hybridization（FISH）

Case reportCase１（Fig．１―４，９，１０，Table１）．A ３０―year―old mother with neurofibromatosis（Reck-

linghausen's disease）admitted because of premature rup-ture of membranes and a female baby was delivered trans-vaginally at ２３ weeks of gestation in １９９０．Neonateweighed５９０g（appropriate for gestational age）and hada minor anomaly of right―sided iris defect. She gained anormal weight increment but was complicated with bron-

chopulmonary dysplasia of IV stage, apnea attack, retino-pathy of prematurity of III stage, cardiac hypertrophy, anddilatation of cerebral ventricles. The placenta weighed５００g（normal range＝１４０±３０g）and the ratio against fe-tal weight reached ０．８５（normal range＝０．２７）．Placentawas half replaced by vesicular chorionic villi, reached upto ２x１cm in diameter. Vesicular villi dispersedly inter-mingled with normal villi in whole placenta, which ne-glected multiple pregnancies. Chorionic stem villi weremicroscopically swollen with central cistern formation butno chorionic epithelial proliferation and atypism werefound. Based on the diagnosis of partial mole, she wastreated with intrauterine curettage and urine b―humanchorionic gonadotropin（HCG）had come down into nor-mal range for ８ months after delivery. Basal body tem-perature（BBT）became biphasic and no silhouette wasfound in chest radiograph. Fluorescent in situ hybridiza-tion（FISH）for formalin―fixed paraffin―embedded speci-mens with anti―centromeres for both X―（red spot）andY―chromosome（green spot）revealed that there were１１３cells with ２ red spots（diploid pattern of４６，XX，９７％）and ４ cells of ３ red spots（triploid pattern of６９，XXX, including X trisomy pattern，３％，Table１）（３，４）．In spite of a chromosomal mosaicism, the previ-ous diagnosis of partial mole was corrected as pseudo―partial mole on the basis of diploid pattern.

Case２（Fig．５―１０，Table１）A ２９―year―old mother delivered female baby，２０６５g

（small―for―date），Apgar９，at３７weeks of gestation in２００２．Placenta weighed９３０g and revealed solid hydropic

Caseexamined nuclei resultstotal numbers X XX XXX

１１８５６８１１３４

％３７％６３％９７％３％

２２８６１４０１４２４

％４９％５１％９７％３％

厚生連医誌第１３巻１号８１～８８２００４

Table１．FISH results for X―and Y―centromeres

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villi, reached up to ５mm in diameter and occupied morethan half volume of placenta. Vesicular villi dispersedlyintermingled with normal villi in whole placenta, whichneglected multiple pregnancies. Stem villous hydropicchange accompanied hypovascular change. Thrombosisand vasculitis were found. There was a small chorioan-gioma up to１．５cm in diameter. There was a weak ten-dency in cistern formation but no trophoblastic epithelialproliferation and atypism could be found. Fluorescent insitu hybridization（FISH）for formalin―fixed paraffin―em-bedded specimens with anti―centromeres for both X―（redspot）and Y―chromosome（green spot）revealed that therewere１４２cells with ２ red spots（diploid pattern of ４６，XX，９７％）and ４ cells of ３ red spots（triploid patternof ６９， XXX, including X trisomy pattern，３％）（３，４）．In spite of a chromosomal mosaicism, the diploidpattern indicated pseudo―partial mole. It was diagnosed aspseudo―partial mole of placenta with chorangioma byMasahiro Nakayama, a pathologist in Osaka Medical Cen-ter and Research Institute for Maternal and Child Health,on the mail consultation of the Japanese Society of Pa-thology.

DiscussionDifferential diagnosis consisted of gestational tro-phoblastic diseases : partial mole and total mole（Table２）（１―３）．A gestational duration of pseudo―partialmole was longer than those of moles, i.e. occurred moreoften in second trimester than in first trimester. Pseudo―partial mole and total mole were genetically diploid butpartial mole was triploid. Moles showed trophoblastic epi-thelial proliferation with atypism. Both pseudo―partialmole and partial mole had evidence of fetus, i.e. nucleatederythrocytes, but total mole lacked it. As to hydropic vil-lous changes in early abortion before an establishment ofhematopoiesis evidence of nucleated erythrocytes was notavailable for reconfirmation of fetus, which required ge-netic analysis for objective diagnostic criteria.Paradinas reviewed the pathognomonic mechanism ofpseudo―partial moles as follows�：half cases of pseudo―partial moles tended to complicate Beckwith―Wiedemannsyndrome, which complicated overgrowth of both fetus,including omphalocele with or without macrosomia, andplacenta because of up―regulation of genes by deregula-tion of the normal expression of imprinted genes. Nor-mally in chromosome１１p the gene of insulin―like growthfactor II（IGF２）as a cell―cycle accelerator was activatedonly in paternal allele and the gene of p５７Kip２ as a cell―cycle repressor was activated only in maternal allele, i.e.imprinted. Conversely in the case of Beckwith―Wiede-mann syndrome IGF２ was up―regulated and p５７Kip２was down―regulated because the imprinted suppression inmaternal allele were replaced by paternal one or therewere two paternal copies of these regions. Pseudo―partialmoles without Beckwith―Wiedemann syndrome had apossibility of minute abnormality at a gene level becausewe could not reveal triploid by usual FISH chromosomalexamination. Genetic rearrangement analysis should bedone with single―stranded conformation polymorphism（SSCP）or restriction fragment length polymorphism

（RFLP）after polymerase chain reaction（PCR）．

References１．Ohyama M et al. Mesenchymal dysplasia of the pla-

centa. PathologyInternational ２０００；５０：７５９―６４．（Their case reportand discussion with３２cases listed from journal ref-erences）

２．Paradinas FJ et al. Pseudo―partial moles : placentalstem vessel hydrops and the association with Beck-with―Wiedemann syndrome and complete moles.Histopathology２００１；３９：４４７―５４．（Database analy-sis at the Trophoblastic Disease Unit at CharingCross Hospital, London，１５cases were listed and dis-cussed the genetic pathogenesis．）

３．Gestational trophoblastic disease , FISH. In :Ikarashi's medical ABC understandable even by a cat―Clinicopathological mechanism and its medicalstrategy―．Ikarashi T. ed．３８th ed. Nagaoka : PimentoPress；２００３（３３．０GB of content）（Soft : Windows.Exel, PowerPoint（Microsoft），Photoshop（Adobe），Ichitaroh（Justsystem），and DocuWorks Desk（FujiXerox））．

４．Mnaual of genetic pathological diagnosis with forma-lin―fixed and paraffin―embedded specimens. Ver．２．eds Genetic examination room in Pathology Centerof Niigata Pref. Health Association, and Chuetus ge-netic diagnosis study group. Nagaoka．２００３．（CD―Ravailable from : URL : http : / / www . Niigata ―kouseiren . jp / hospital / byouri２／site％２０one / top .htm）．

和文抄録

偽部分奇胎の２症例

病理センター、病理科；病理医１）、遺伝子診断室（中越遺伝子診断研究会）；臨床検査技師２）五十嵐俊彦１）、長谷川秀浩２）

背景：絨毛性疾患でない偽部分奇胎が部分奇胎として治療されている。無用な治療を避ける意味で、偽部分奇胎の疾患概念の普及と診断確立が望まれている。症例：妊娠中期と後期まで妊娠が継続した偽部分奇胎の２症例を経験したので報告した。各症例の出生時女児体重は正常範囲でBeckwith―Wiedemann 症候群は認められなかった。胎盤は重く、びまん性・散在性に胎盤全体に水腫様幹絨毛が認められた。胎盤絨毛の染色体は fluorescence in situ hybridization（FISH）検査上、二倍体の４６，XXと判断された。顕微鏡所見上、絨毛上皮細胞の増生と異型性は認められなかった。以上より、本症例は偽部分奇胎（別称：胎盤幹血管水腫、胎盤間葉異形成など）と診断された。結論：妊娠早期における奇胎からの偽部分奇胎の組織学的診断は困難な場合が多く、FISH による染色体検査は補助診断として極めて有効であった。

キーワード：偽部分奇胎、胎盤幹血管水腫、胎盤間葉異形成、絨毛血管腫、二倍体、蛍光 ISH（FISH）


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classifica-

tion

histology

trophoblasticdisease

non－trophoblastic

trophoblastic

molar

molar

nonmolar

villous

implantation

site

chorionic

―type

cytotro-

phoblast

syncytiotro-

phoblast

mole

invasive

choriocarci-

noma

implantationsiteITinan-

choringfoci

chorionic－type

ITin

laeve

pseudo

－partilalmolepartial

complete

exaggerated

placental

site

placental

site

tro-

phoblastic

tumor

placental

sitenodule

epithelioid

trophoblas-

tictumor

develop-

mentalge-

netics

diploid

triploid

６９XXY（di-

andry）＝

dispermy

（２３X＋２３

Y）＋egg（２３

X）

diploid

４６XX，４６

XY（dian-

dry）＝dis-

permy（２３

X，２３Y）＋

emptyegg

presentation

３rd＜２nd

＜１st

trimester

１sttrimes-

ter

１sttrimes-

ter

aftermole

missed

abortion

spotting

embryo

＋＋

－

villousout-

line

scalloped

scalloped

round

trophoblast

proliferation

－focal,mini-

mal

variable

,marked

trophoblas-

ticatypism

－－

often

p５７（kip

２）

＋,diffuse

－／weak

villi

＋＋

＋＋

－－

－－

－

terminalvil-

lous

hy-

drops

weak

＋＋

＋

terminalvil-

louscistern

－＋

＋＋

trophoblas-

ticinclusion

－＋

stemvillous

hydrops

＋possible

possible

possible

stemvillous

aneurysmal

dilatation

＋－

－－

stemvillous

peripheral

chorioan-

giomatoid

＋－

－－

extramedul-

laryhema-

topoiesis

＋－

－－

Table２．Clinico―pathological differential diagnosis for gestational trophoblastic diseases.


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classifica-

tion

histology

trophoblasticdisease

non－trophoblastic

trophoblastic

molar

molar

nonmolar

villous

implantation

site

chorionic

―type

cytotro-

phoblast

syncytiotro-

phoblast

mole

invasive

choriocarci-

noma

implantationsiteITinan-

choringfoci

chorionic－type

ITin

laeve

pseudo

－partilalmolepartial

complete

exaggerated

placental

site

placental

site

tro-

phoblastic

tumor

placental

sitenodule

epithelioid

trophoblas-

tictumor

cell

dimorphic:

primitive

previllous－

type

tro-

phoblastic

monomor-

phic

IT,

large,pleo-

morphic

,abundant,

eosinophilic

monomor-

phic

IT,

small,

round,uni-

form,

eosinophilic

orclear

infiltration

expansile

,dimorphic

infiltrating

single

cell

orconfluent

cells

expansile

epithelioid

nestorcord

orsolid

mass

necrosis

++－

++

calcification

－－

＋

vascularin-

vasion

fromlumen

toperiphery

fromperiph-

erytolu-

men

－

fibrinoid

－＋

＋

mitosis／１０

HPF

２－２２

０－６

１－１０

HLA－G

++++

++++

+++eosino-

philiccyto-

plasm

－－

+inIT

++++

++++

++++

ineosinophilic

cytoplasm

++++

ineosinophilic

cytoplasm

b－HCG

－－，

＋inmultinu-

cleatedIT

－－

++++

+inST

－+inmulti-

nucleatedIT－

－

inhibin－

a－

＋＋

＋＋

CK－１８

－＋

＋＋

＋

HPL

－／＋＋

towarddis-

talend

++++

－／＋

－++++

+inIT

＋＋

－／focal

－／focal

Mel－CAM,

CD１４６

－／＋＋＋

＋toward

distalend

++++

－／＋

－－

+inIT

＋＋

－／focal

－／focal

PlAP

－－

+++

－－

－－／＋

－／＋

+/++

+/++

Ki－６７

in-

dex

９０％＜

０３－１０％

２５－５０％

０９０％＜単核

＜１％

１０％＜

＜１０％

１０－２０％

chemother-

apyeffect

good

variable

variable

treatment

chemotheray

hysterec-

tomy

hysterec-

tomy


― 84 ―

Fig１．Case１．Enlarged placenta consisted of nor-mal villi intermingled with vesicular ones, thelatter of which occupied around half volumeof placenta. Vesicular diameter reached up to１cm in close―up picture.

Fig２．Case１．Stem villous hydropic change and cistern formation on scanningmicroscopy, graduated in millimeters.

Fig３．Case１．Stem villous hydropic change without any trophoblastic epithelialproliferation and atypism, scaled ２mm in length.


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Fig４．Case１．Most chorionic cells had two red spots in FISH.

Fig５．Case２．Enlarged placenta consisted of normal villi intermingled with vesicular ones, the latter of whichoccupied more than half volume of placenta.


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Fig６．Case２．Stem villous hydropic change withhypovascular change. Thrombosis（arrow）and vasculitis（arrow head）were found,graduated in millimeters or bar of ２mm inlength.

Fig７．Case２．Stem villous hydropic change was confirmedwith hypovascular change and cistern formation withoutany trophoblastic epithelial proliferation and atypism,scaled ２mm in length. Chorangioma was found in theleft picture.


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Fig８．Case２．Most chorionic cells had two red spots in FISH.

Fig９．Fetal weight of pseudo―partial mole from refer-ence, which was limited within normal range.Closed circle（●）was complicated with Beckwith―Wiedemann syndrome and open circle（○）wasfree from this syndrome�．There was no signifi-cant difference between them. Our Case１（▽）and Case２（△）were also drawn.

Fig１０．Placental weight of reported cases was veryheavy�．Symbol marks were same as above andno statistical difference was found.


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