http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, 2014; 27(10): 1055–1063 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2013.847424
ORIGINAL ARTICLE
Placenta chorioangioma: a rare case and systematic review of literature Bassel H. Al Wattar1, Sarah C. Hillman1,2, Tamas Marton3, Katharine Foster4, and Mark D. Kilby1,2
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1
Fetal Medicine Centre, Birmingham Women’s Foundation Trust, Birmingham, UK, 2Centre for Women’s & Children’s Health, The School of Clinical and Experimental Medicine, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham, UK, 3Department of Perinatal Pathology, Birmingham Women’s Foundation Trust, Birmingham, UK, and 4Department of Pediatric Radiology, Birmingham Children’s Hospital, Birmingham, UK Abstract
Keywords
Objectives: Placental chorioangioma is a relatively rare condition that often results in serious prenatal complications and adverse pregnancy outcome. We report a case of a large chorioangioma that was prenatally diagnosed at 23 weeks with polyhydramnios and fetal anemia. With prenatal monitoring, transplacental therapy with a COX-2 inhibitor and intrauterine transfusion, the pregnancy resulted in the live birth at 30 weeks. Due to the paucity of evidence relating to the management protocols in cases of placental chorioangiomas, we have conducted a systematic review of the literature. Methods: All reported cases in the English language were captured using the electronic databases. Bibliographies of relevant articles were manually searched. Results: Sixty-four articles were included reporting 112 cases of placental chorioangioma. In 79, there was no prenatal treatment and in 33 there was in-utero treatment. A systematic comparison of antenatal complications and pregnancy outcomes was performed. No strong conclusion could be made due to the low number and quality of the reported cases. Conclusion: Placenta chorioangioma represents a challenge with its potentially serious complications adversely affecting pregnancy outcome. An international registry of pregnancies with this rare complication and documentation of pregnancy outcomes will improve the evidence base for prospective management.
Choriangioma, colour Doppler, intrauterine treatment, placenta, systematic review, tumor, ultrasound
Introduction Placental chorioangioma is the most frequent nontrophoblastic benign tumor of the placenta, reported to be present in about 1% of placentas examined by microscopy. However clinically evident, so-called ‘‘Giant’’ tumors are less common with an estimated incidence of between 1:3500 and 1:9000 births [1]. While the majority of tumors maybe asymptomatic in pregnancy (particularly when 54 cm), a significant proportion are reported as being associated with a number of serious antenatal complications such as fetal anemia, hydrops fetalis, polyhydramnios, antepartum hemorrhage, preterm labor and birth, intrauterine fetal growth restriction (IUGR) and increased perinatal mortality rates [2]. Early antenatal diagnosis, assessment and the possibility of intrauterine treatment could play a vital role in improving the pregnancy outcome. While different treatment methodologies have been reported and systematic reviews of the literature performed, absolute numbers remain small and there is no
Address for correspondence: Professor Mark D. Kilby, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK. Tel: 0121 627 2778. Fax: 0121 623 6875. E-mail: [email protected]
History Revised 30 April 2013 Accepted 18 September 2013 Published online 17 October 2013
strong evidence to support superiority of any single treatment [3,4] in terms of improving pregnancy outcome. We report a prenatally detected case of a large placental chorioangioma highlighting the importance of close surveillance, individualized pregnancy assessment to tailor therapy and early intervention.
Case report Mrs HM was a 26-year-old finance officer referred from her local district general hospital at 23 weeks and 4 days. She had a pre-pregnancy weight of 47.7 kg, a height of 157.5 cm, giving her a body mass index of 19.2. Her blood group was A Rhesus positive. She had a previous uncomplicated pregnancy in 2010 when she gave birth to a term baby weighing 3.6 kg. After referral, a detailed ultrasound scan at the tertiary Fetal Medicine Centre at Birmingham Women’s Foundation Trust, United Kingdom demonstrated an appropriately grown fetus (estimated fetal weight 536 g) with no fetal abnormality. The amniotic fluid volume was increased with a maximum pool depth of 7 cm. The placenta was relatively homogenous but a discrete, well circumscribed mass measuring 7 4 3 cm, adjacent to the umbilical cord insertion, that had the appearances of a placental Chorioangioma was noted (Figure 1). Colour flow Doppler demonstrated several large
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Figure 1. The placental chorioangioma on ultrasound.
‘‘vessels’’ running from the placental umbilical cord insertion and the tumor. Fetal Doppler waveforms demonstrated that the peripheral and intracardiac arterial and venous velocities were normal, with no evidence of fetal anemia and at that stage no evidence of cardiodynamic dysfunction. An oral glucose tolerance test excluded glucose intolerance and maternal serology for cytomegalovirus and toxoplasmosis demonstrated no abnormality. Serial ultrasound scans at weekly intervals were performed. At 25 weeks and 2 days, the liquor volume was noted to have increased significantly to a maximum pool depth of 10 cm. Again, Doppler assessment of the Ductus Venosus waveform demonstrated positive flow during atrial contraction and the umbilical artery Doppler velocity showed positive end diastolic flow. The middle cerebral artery peak systolic velocity was within normal limits for gestation. Maternal blood pressure remained normal at 120/80 mm/Hg and there was no proteinuria on urinalysis. The patient was started on Sulindac (a COX-2 inhibitor) at a dose of 200 mg twice daily orally. A fetal MRI confirmed the presence of a ‘‘well-defined lesion of homogenous signal in the caudal aspect of the placenta, close to the placental umbilical cord insertion’’ (Figure 2). This placental lesion measured 60 60 43 mm and appears to have a prominent vessel at its inferior aspect extending through it to the insertion of the umbilical vessels (within a centimeter of the tumor). It contained areas of ‘‘high T1 signal suggesting some hemorrhage within the lesion’’. The lesion also demonstrates restricted diffusion suggesting ‘‘high cellularity’’. With continuing maternal Sulindac therapy and regular review, the maximum pool depth of liquor decreased to 7 cm and this along with fetal biometry and peripheral and intracardiac arterial venous Doppler measurements were measured at weekly intervals and remained within normal limits for gestation. At 26 weeks of gestation a maternal course of prophylactic Betamethasone was given. At 27 weeks and 5 days, the maximum pool depth of amniotic fluid had decreased to 5 cm and therefore the Sulindac was discontinued. The patient remained normotensive. At 28 weeks and 2 days the patient was rescanned. The fetus had an
Figure 2. A (FIESTA) MRI section of the placental chorioangioma.
estimated fetal weight of 963 g and was below the 10th centile on customized growth charts. The maximum pool depth of liquor volume remained at 6 cm. However, the middle cerebral artery peak systolic velocity had increased and was elevated at 72 cm per second (41.5 MoM). The Ductus Venosus waveform demonstrated an elevated PVIV but there was positive flow during atrial contraction. There were also positive end diastolic velocities on umbilical artery Doppler insonation. The patient was rescanned 48 h after this and in addition to an elevated middle cerebral artery peak systolic velocity (greater than 1.5 multiples of the median) a small pericardial effusion had developed. The liquor volume had also increased so that the maximum pool depth was 7 cm and therefore maternal Sulindac therapy was reintroduced at a dose of 200 mg twice daily orally. A maternal Kleihauer test demonstrated no evidence of significant transplacental hemorrhage. Because of the associated risks of fetal anemia and placental chorioangioma, donor erythrocyte packed cells (irradiated and leuco-depleted) were prepared and percutaneous fetal blood sampling performed by cordocentesis of the placental cord root. The fetal hemoglobin was 6.3 g/dl (55 standard deviations from the mean for gestation) and the fetal platelet count was 435 109/L with a reticulocyte count of 12%. Transfusion of 50 ml of 80% hematocrit red packed cells was given to increase the fetal hemoglobin to 12.6 g/dl. Post-transfusion, a further fetal MRI scan was performed and again demonstrated a mass arising from the placenta at the site of the umbilical cord insertion. This had increased in size, measuring 8 7 5.8 cm. At 30 weeks and 2 days, a repeat ultrasound scan demonstrated the complete resolution of the pericardial effusion but a small rim of abdominal ascites. The fetus remained growth restricted but the umbilical artery Doppler velocimetry was within normal limits and the ductus venosus waveform showed positive flow during atrial contraction. A further course of maternal Betamethasone was given.
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Search methodology Our systematic review followed a prospective protocol developed using widely recommended and comprehensive methodology [9].
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Data sources
Figure 3. Photo of the placenta with the chorioangioma post-delivery.
A search strategy was developed based on existing advice for prevalence searches [10]. All the reported cases of placental chorioangiomas in English language were captured using the electronic databases MEDLINE (1966–Dec 2012), Embase (1980–Dec 2012), Cochrane Library (1999–Dec 2012). Bibliographies of relevant articles were manually searched to identify papers not captured by electronic searches. Eligibility criteria for selecting studies
A non-stressed cardiotocograph (CRT) demonstrated a fetal heart rate of 165 beats per minute with a short-term FHR variation measured at 510 ms. Because of fetal growth restriction, a rim of ascites and the reduced short-term variability on the CTG multidisciplinary discussion with our neonatal pediatric colleagues occurred. After this it was decided to deliver this fetus by emergency cesarean section. A live born baby girl weighing 1455 g was delivered. She had an Apgar score of 8 at 1 min and 10 at 5 min. The placenta was sent for histology (Figure 3). Macroscopic examination revealed a 16 13 3 cm placenta weighing 478 g with a pale, brown and homogenous tumor measuring 9 7 4 cm. Histological examination confirmed that the tumor is chorioangioma with signs of necrosis and dystrophic calcifications. The tissue show mostly capillary vascular proliferation with fibrotic connective tissue in between. Over the preceding 3 weeks the baby continued to gain weight and was discharged back to the local district general hospital for special care support. The baby continues to thrive and is alive and well. Systematic review of evidence for treatment of placental chorioangioma While the incidence of placental chorioangiomas is relatively low, its diagnosis and management represent a challenge due to its progression to antenatal complications and the increased risk of a poor pregnancy outcome. Early specialist scanning is important in managing placental chorioangiomas allowing early and prompt management of cases [5]. In our case, the patient had intensive and close surveillance with advanced scanning techniques that allowed early management with intrauterine treatments to prolong gestation and attempt to improve the fetal outcome. There have been several contemporary reviews of the literature examining the treatment in this potentially morbid condition [4,6]. These literature reviews highlight the nature of the small cohort studies available to give evidence base to these treatments and the heterogeneity of treatment choices. We performed a systematic review of the available literature which both updates available literature reviews and also uses methodology described according to STROBE and MOOSE criteria [7,8].
All reported cases were included and only opinion articles were excluded. Figure 4 shows the process of study selection. Reference lists were hand searched for relevant articles for inclusion. Inclusion and exclusion of papers was performed by two reviewers (B. H. W. and S. H.), any differences were resolved by a third reviewer (M. D. K.). Quality assessment and data synthesis STROBE was used to generate quality assessment of primary studies included [7] (Figure 5). Data were extracted into Excel tables and statistical analysis was performed using Fisher’s exact test as further described in the results.
Results Sixty-four articles were included in the systematic review reporting 112 cases of prenatally diagnosed placental chorioangioma. Of these, 79 did not have any treatment and 33 had prenatal interventions. From the literature, the mean gestational age at diagnosis was 28.5 weeks (range 16–40 weeks) and mean gestational age at delivery was 33.7 years (range 19–40 years). The mean size of the reported tumor was 60 mm (at the largest diameter) (range 20–200 mm). Comparison between prenatal treatment and non-treatment group A comparison of antenatal complications and outcomes between the treatment versus non-treatment group is highlighted in Table 1. The disease related antenatal complication rate (Fishers exact test, p ¼ 0.0004) appears to be higher in the treated group (prior to treatment) compared to the non-treated group. This was likely to be secondary to case selection, with those pregnancies deemed to be at risk being those in which invasive treatment was advocated. In addition, though, invasive treatment will carry a risk of iatrogenic fetal morbidity and mortality. All pregnancies resulting in live babies were considered to have good outcome. The complications of IUD, early neonatal death and admission to NICU were reported separately (Table 1). There was no difference in pregnancy outcome between treated and non-treated groups (Fishers exact test comparing good outcome of pregnancy, p ¼ 0.82).
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Figure 4. Process from initial search to final inclusion for systematic review of cases of placental chorioangioma.
Figure 5. Quality assessment of included paper using the STROBE checklist.
This could suggest that overall treatment/intervention may improve the outcome (as this group had more complications), but that the numbers are two small to draw any definite conclusions.
Comparison between specific treatment modalities The frequency of different treatment methods used and reported in the literature is demonstrated in Table 2.
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Table 1. Comparison of complications and outcomes between the treatment and non-treatment groups.
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Treatment group (need %)
Non-treatment group (need %)
p Value 1.0000 0.0004 0.0002 0.0004 1.0000 0.0015 0.5546 0.1392
MRI performed for diagnosis Antenatal complications Polyhydramnios Sings of hydrops IUGR Fetal anemia Placental abruption Pre term delivery
0/33 33/33 26/33 20/33 5/33 10/33 0/33 24/33
2/79 58/79 31/79 19/79 11/79 5/79 3/79 45/79
Admission to NU
Not reported 11 No 13 Yes 9
Not reported 21 No 39 Yes 19
Fetal outcome
Died 5/33 Good 23/33 Not reported 1/33 Stillbirth 4/33
Died 9/79 Good 57/79 Not reported 2/79 Stillbirth 11/79
1600 g ELSCS ¼ 6/33 EMLSCS ¼ 3/33 IOL ¼ 3/33 Not reported ¼ 1/33 NVD ¼ 20/33 TOP ¼ 0/33
1592 g ELSCS ¼ 7/79 EMLSCS ¼ 17/79 IOL ¼ 5/79 Not reported ¼ 0/79 NVD ¼ 47/79 TOP ¼ 3/79
Average birth weight MOD
0.5494 0.8210 1.0000
IUGR, intrauterine growth restriction; NU, neoonatal unit; MOD, mode of delivery; ELSCS, elective lower segment caesarean section; EMLSCS, emergency lower segment caesarean section; IOL, induction of labour; NVD, normal vaginal delivery; TOP, termination of pregnancy. Table 2. The frequency of treatment modalities in reported cases. Treatment mode Amnioreduction IUT Digoxin Laser ablation Alcohol injection ablation Bipolar coagulation Radiofrequency ablation Surgical clip application Surgical ligation Embolization
Frequency of cases 10 6 5 8 4 5 2 1 1 3
The pooled data set was too small to draw meaningful and significant conclusions in favour of one treatment modality over another. A brief narrative review of each treatment case is described in Table 3. The number of cases reported in the literature before the year 2000 was 54 with 11 cases treated (20.3%). This is in comparison to 59 cases reported after the year 2000 with 22 cases treated (37.2%).
Discussion This critical appraisal and systematic review of the literature complements those previously performed and highlights that prenatally diagnosed large placental chorioangioma are associated with a high incidence of antenatal complications. This highlights the importance of early diagnosis, individualized assessment and the consideration of in-utero management in such cases. Presently ultrasound and to a much lesser extent, in-utero magnetic resonance imaging (MRI), are the options of choice for imaging the placenta [11].
Colour flow and power-Doppler have made diagnosis more specific, have allowed the vascularity of the tumor to be assessed and may also allow the detection of angiomatous cellular and degenerative change [12]. Colour Doppler can be further used to visualize a discrete ‘‘feeding vessel’’, with consideration of vascular-occlusive therapy such as injection of sclerosing agents or fetoscopic laser ablation [4,13,14]. Successful prenatal intervention may be primarily achieved in those cases in which the chorioangioma is located away from the umbilical cord insertion site and by ‘‘Doppler mapping’’ noting that the circulation is not directly dependent on the umbilical cord. Peripheral and intrafetal arterial and venous Doppler imaging is also important in observing the response to treatment [11]. In our case, the fetus demonstrated no objective intracardiac findings of dysfunction and the very close proximity of the giant chorioangioma to the cord insertion gave cause for concern that feeding vessels may be multiple and large in size, making endoscopic laser coagulation more difficult and in all likelihood associated with complications such as vessel bleeding. Placental MRI has recently been reported as being used as an adjunct to ultrasound placental imaging [15]. This modality is safe in pregnancy, offers information about the maternal anatomy, the placental site and it has an ability to differentiate between different placental pathologies by Tweighting of the image. It may offer additional information to the clinician, guiding the management of such cases [11]. In our case study, the use of MRI offered accurate information about the nature of the placental mass, its size and position. From this perspective, it added little to the objective diagnosis but comments on T1/T0 weighing and cellularity were of interest and may be able to give information on differentiation between chorioangiomas and
Year of publication
2012
1998
2007
2003
2007
2006
1999
2003
2000
2000
2000
2003
2005
Author
Babic
Bashiri
Bermudez
Bhide
Deren
Esscribano
Haak
Hamill
Jauniaux
Jauniaux
Jauniaux
Kin Lau
Kin Lau
Polyhydramnios at 28 weeks. Preterm labour at 36 weeks. Polyhydramnios at 29 weeks. Preterm labour at 34 weeks. Polyhydramnios at 26 weeks. Oligohydramnios, MPD 3.7 cm þ fetal cardiomegaly þ fetal anemia at 24 weeks. Preterm labour at 29 þ 6 weeks. APH at 24 weeks, hydropic fetus þ generalized skin oedema þ bilateral pleural effusion þ pericardial effusion þ placentomegaly þ cardiomegaly þ polyhydramnios (AFI ¼ 21)
30 30 30 mm
200 180 170 mm.
100 80 60 mm
40 50 50 mm
Embolization with 1.5 mL of enbucrilate at 24 þ 2 weeks.
Amnioreduction at 26 weeks, repeated at 30 weeks. Intrauterine transfusion at 24 weeks and embolization intrauterine transfusion repeated at 27, 28 and 29 weeks.
Amnioreduction at 29 weeks
Intrauterine transfusion with 60 mL of Onegative blood at 25 weeks. Amnioreduction at 28 weeks
IUT with 100 ml of packed red cells.
IUT performed with 60 ml RBC at 16 weeks, Polyhydramnios þ pericardial effusion þ elevated MCA Ps persisted, alcohol injection into the tumor twice at 24 and 25th week. IUT at 25 weeks.
LSCS for breech presentation at 39 weeks, Female infant 3270 g good fetal outcome. Pre term at 32 weeks, NVD of female baby 2957 g, admitted to NNU for prematurity þ had about 25 small cutaneous hemangiomas spread over her body. Ultrasound examination of the heart showed ventricular hypertrophy. Discharged after 27 days. Induction of labour at 36 þ 4. Live baby, good outcome. Spontaneous Live baby of 3120 g. vaginal delivery at 36 weeks. Good outcome. Spontaneous Live baby of 2220 g. vaginal delivery at 34 weeks. Good outcome. Spontaneous Live baby of 3140 g. vaginal delivery at 38 weeks. Good outcome. An emergency classical caesarean section at 29 þ 6 for fetal malpresentation, a 1.185 kg baby was delivered. NND day 2 of life. SROM þ preterm at 26 weeks, breech position, emergency LSCS. baby girl weighed 845 g. Good outcome.
Live female delivered by elective lower segment caesarean at 32 weeks. Admitted to NNU for 3 weeks. Good outcome. Pre-term labour at 28 weeks, NVD with female infant of 1330 g, admitted to NNU for surfactant treatment. Discharged after 15 days.
IUD at 26 weeks.
YAG Laser ablation þ IUT þ amnioreduction at 24 weeks. IUT was repeated at 25 weeks. Interstitial laser at 24 weeks, repeated at 26 weeks.
Live male of 995 g. NND at? weeks
Amnioreduction at 24 weeks.
Postnatal outcome live female baby of 1.6 kg delivered by elective Caesarean section at 30 þ 4. Admitted to the NNU for 42 days. Good outcome.
Treatment performed Amnioreduction þ percutaneous embolization of the tumor by injecting enbucrilate (Histoacryl; n-butyl-2-cyanoacrylate liquid adhesive glue) Intrauterine transfusion with 50 mL of O-negative blood.
Placenta chorioangioma
20 20 30 mm
Fetal anemia at 25 weeks
60 64 45 mm
Mild cardiomegaly þ moderate/severe anemia at 25 weeks. Preterm @ 30 weeks þ polyhydramnios, þ Cardiomegalyþ hepatosplenom galy þ fetal anemia.
Polyhydramnios þ cardiomegaly þ pericardial perfusion þ dilatation of the hepatic vein suggesting heart failure þ fetal anemia at 16 weeks.
53 45 44 mm
53 48 61 mm
71 81 45 mm
72 83 mm
Antenatal complications Polyhydramnios at 22 weeks (MPD ¼ 13 cm). 30 weeks and 2 days of gestation, an ultrasound detected poor fetal right ventricular contractility with enlarged thick ventricular walls and mild pericardial effusion Polyhydramnios at 22 weeks. Preterm labour at 27 weeks Polyhydramnios, (MPD 12 cm) þ scalp edema and Ascites þ reversed flow in the ductus venosus þ fetal anemia at 24 weeks. Mild cardiomegaly at 23 weeks with hyperdynamic Circulation. IUGR at 26 weeks.
42 56 58 mm
Size of placental chorioangioma
Table 3. Brief summary of treated cases.
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1999
2005 1996
2003
2003
2009
2009
2009
1996
2002
2012
2002
2002
2002
2002
Nicolini
Quarello Quintero
Sepulveda
Sepulveda
Sepulveda
Sepulveda
Sepulveda
Wang
Wanapirak
Yen Lim
Zalel
Zalel
Zalel
Zalel
Polyhydramnios at 23 weeks. Fetal scalp oedema þ pericardial effusion þ Pleural effusion þ normal EDF in MCA at 24 weeks. Severe polyhydramnios at 26 weeks Polyhydramnios, hydrops, cardiac failure at 23 weeks. None.
38 34 44 mm 85 mm
75 56 mm
40 mm
70 mm
50 mm
130 mm
Mean of 83 mm
2 encapsulated masses: 1st 60 mm, 2nd 40 mm.
110 65 30 mm
Hydrops fetalis at 25 weeks.
Polyhydramnios at 21 weeks. Pre term at 26 weeks.
Polyhydramnios, pericardial effusion, cardiomegaly at 28 weeks. Polyhydramnios, hydrops fetalis at 29 weeks.
Polyhydramnios þ cardiomegaly þ pleural effusion þ ascites þ oedema of scalp at 24 weeks. Preterm labour at 25 weeks. Polyhydramnios þ signs of hydrops fetalis þ cardiomegaly þ minimal pericardial effusion þ mild ascites and a dilated intra-abdominal umbilical vein (8 mm) þ absent end diastolic flow at 27 weeks. Pre term at 32 weeks. 8 Cases diagnosed, 6 had polyhydramnios, 3 had non-immune hydrops and 5 had high cardiac output state.
Polyhydramnios with MPD ¼ 12 cm, short cervix of 22 mm with funnelling þ fetal anemia at 20 weeks. Pre term Labour at 28 weeks. Severe polyhydramnios and fetal hydrops at 20 weeks.
Polyhydramnios þ fetal anaemia at 22 weeks.
50 45 40 mm
68 60 mm
Polyhydramnios þ fetal anaemia at 25 weeks.
60 35 30 mm
Digoxin.
Amniocentesis þ digoxin.
Indometacin þ digoxin
Post-operatively, 80% survival rate, hydrops resolved in 2 of 2, cardiac output normalized in 4 of 4. All were live born at mean gestational age of 35.4 weeks. Five patients had fetoscopic devascularization. mean gestational age of 23.9 weeks. Bipolar coagulation (n 1), combination of bipolar and diode laser (n 2), bipolar and radiofrequency ablation (n 1), and surgical clip application (n 1). Digoxin.
Spontaneous vaginal delivery at 38 weeks. Good outcome. Premature rupture of membrane þ Spontaneous vaginal delivery at 26 weeks. Spontaneous vaginal delivery at 37 weeks.
Fetal demise at 33 weeks.
spontaneous vaginal delivery 32 weeks, female baby of 1360 g. Good outcome.
NVD at 25 weeks, died at 54 days.
Fetal demise at 29 weeks.
Emergency caesarean section 37 weeks for previous section, 3460 g female baby, good outcome. Emergency caesarean section 1150 g female baby delivered Died at 1 year of age due to an episode of acute renal insufficiency.
Spontaneous vaginal delivery at term. Good outcome. Fetal demise at 26 weeks.
Spontaneous vaginal delivery. Good outcome. Spontaneous vaginal delivery. Good outcome. LSCS at 39 weeks for breech, good out come IUD 3 days after treatment.
Alcohol ablation at 27 weeks.
Combined sonographic- and endoscopic guided intra-tumoral interstitial laser ablation at 28 weeks. Amniocentesis for karyotyping þ Digoxin given to mother at 24 weeks.
Intrauterine transfusion þ endoscopic laser coagulation.
Endoscopic laser coagulation þ amnioreduction at 24 weeks
Alcohol injection at 26 weeks.
Alcohol injection at 24 weeks. Repeated at 25 weeks. Laser ablation þ Amnioreduction. Ligation of feeding vessel to chorioangioma with 3-0 vicryl. þ bipolar coagulation to the rest of the feeding vessels. Amnioreduction at 27 weeks
Alcohol injection at 27 weeks.
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A number of these cases have been reported previously in a number of literature reviews (2;4;21).
1999
Nicolini
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other placental masses such as haematoma (avascular), subchorionic fibrin (avascular), partial mole, hydropic degeneration, degenerating fibroid or placental teratoma [9]. However in our systematic review of the literature, the use of prenatal MRI, despite its non-invasive character was restricted to two cases and probably reflects clinician scepticism that this imaging modality adds important information. There is little consensus in the literature about the association between the chorioangioma size and its clinical manifestations. While many authors considered placental chorioangiomas to be clinically significant when larger than 4 cm (4;12) others suggested a ‘‘cut off’’ of 5 cm [16–18]. This systematic review noted that in 99 of the 112 cases reported the size of the chorioangioma was documented. In nine reported cases (9/99; 9.0%), the placental chorioangiomas was less than 4 cm. Four of these ‘‘small tumors’’ (4/9; 44%) had co-exiting fetal complications, but all had a good perinatal outcome. When the placental tumor was reported as measuring between 4 and 5 cm (12/99; 12.2%), all had perinatal complications and in three this was associated with a stillborn baby (25%). While in the 78 cases the ‘‘tumor’’ was reported to be 45 cm (78/99; 78.8%). In this cohort, there was with a reported fetal and perinatal mortality of 28.2% (13 fetal deaths and 9 stillbirths). Anecdotal descriptions, within relatively small case cohort studies, of invasive, in-utero treatment have been described. One of the earliest was by Quintero et al. in 1996 performing open surgical ligation of the feeding vessel to the chorioangioma. This intervention, perhaps unsurprisingly was associated with a poor outcome resulting in intrauterine death [19]. Subsequently, several types of in-utero, experimental treatment have been described with no strong evidence that one treatment modality is superior to any other. In our case study, we describe the use of the COX-2 inhibitor, Sulindac. This was utilized as there was associated polyhydramnios (with objective evidence of fetal cardiac compromise). The associated polyhydramnios has been linked to the tumor vasculature behaving as a vascular shunt predisposing to high cardiac output secondary to reduced fetal afterload. Indeed, there is evidence in the literature that such medical therapy may prolong gestation and therefore increased survival [20]. As already stated, the use of fetoscopic laser ablation of the ‘‘feeding vessel’’ to the large tumor was not performed in this case. The risks of the procedure in terms of vessel bleeding during laser ablation, due to the presence of multiple vessels and the close proximity of the tumor to the umbilical cord insertion were considered relatively contraindication (when the fetus was not demonstrating signs of cardiac dysfunction). The complication of fetal anemia has been described, in up to 15% of cases and has led to the use of serial middle cerebral artery peak systolic velocity measurements to screen for this complication [3]. In our case, intravascular, in-utero transfusion was the only invasive therapy used. Our systematic review of the literature, did not conclusively demonstrate the benefit of treatment over conservative management in improving the fetal and neonatal mortality. However, the numbers in this review are relatively small and
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bias of treatment in the most compromised babies is likely to be a confounding factor. Other outcomes such as neonatal morbidity need for emergency caesarean sections, resolution of polyhydramnios and hydrops were difficult to be analyzed due to the small number of reported cases. Prenatal treatment may be classified as (a) supportive (i.e. intrauterine transfusion, amnioreduction or by using transplacental pharmacotherapy) and (b) definitive treatment (i.e. surgical ligation/clipping, fetoscopic laser ablation, embolization, alcohol injection and radiofrequency ablation). Small number of cases, operator bias and low-quality information described in some papers (due to detailing of techniques) mean that no conclusive proof of benefit can be demonstrated. However, it is likely that therapy is only contemplated when there are ultrasound features of fetal compromise and the gestation is non-viable. These data indicate the need for an international register to document management in such cases and accurately record complications of therapy and perinatal outcome.
Declaration of interest All authors report no conflicts of interests. The authors alone are responsible for the content and writing of this article.
References 1. Guschmann M, Henrich W, Dudenhausen JW. Chorioangiomas– new insights into a well-known problem. II. An immunohistochemical investigation of 136 cases. J Perinat Med 2003;31: 170–5. 2. Sepulveda W, Alcalde JL, Schnapp C, Bravo M. Perinatal outcome after prenatal diagnosis of placental chorioangioma. Obstet Gynecol 2003;102:1028–33. 3. Zanardini C, Papageorghiou A, Bhide A, Thilaganathan B. Giant placental chorioangioma: natural history and pregnancy outcome. Ultrasound Obstet Gynecol 2010;35:332–6. 4. Sepulveda W, Wong AE, Herrera L, et al. Endoscopic laser coagulation of feeding vessels in large placental chorioangiomas: report of three cases and review of invasive treatment options. Prenat Diagn 2009;29:201–6. 5. Wou K, Chen MF, Mallozzi A, et al. Pregnancy outcomes and ultrasonographic diagnosis in patients with histologically-proven placental chorioangioma. Placenta 2011;32:671–4. 6. Amer HZ, Heller DS. Chorangioma and related vascular lesions of the placenta–a review. Fetal Pediatr Pathol 2010;29:199–206. 7. von EE, Altman DG, Egger M, et al. Strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Br Med J 2007; 335:806–8. 8. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. J Am Med Assoc 2000;283:2008–12. 9. Khan, Khalid S, Gerben Ter Riet, et al. Undertaking systematic reviews of research on effectiveness CRDs guidance for carrying out or commisioning reviews. CRD report No 4, 2nd edn. NHS centre for reviews and dissemination; University of York; 2011. 10. Glasziou P IlBCCG. In PDQ evidence-based principles and practice. 1999. Hamilton Canade. 11. Abramowicz JS, Sheiner E. In utero imaging of the placenta: importance for diseases of pregnancy. Placenta 2007;28:S14–22. 12. Wehrens XH, Offermans JP, Snijders M, Peeters LL. Fetal cardiovascular response to large placental chorioangiomas. J Perinat Med 2004;32:107–12. 13. Bhide A, Prefumo F, Sairam S, et al. Ultrasound-guided interstitial laser therapy for the treatment of placental chorioangioma. Obstet Gynecol 2003;102:1189–91.
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14. Nicolini U, Zuliani G, Caravelli E, et al. Alcohol injection: a new method of treating placental chorioangiomas. Lancet 1999;353: 1674–5. 15. Blaicher W, Brugger PC, Mittermayer C, et al. Magnetic resonance imaging of the normal placenta. Eur J Radiol 2006;57:256–60. 16. Wanapirak C, Tongsong T, Sirichotiyakul S, Chanprapaph P. Alcoholization: the choice of intrauterine treatment for chorioangioma. J Obstet Gynaecol Res 2002;28:71–5. 17. Hata T, Inubashiri E, Kanenishi K, et al. Three-dimensional power Doppler angiographic features of placental chorioangioma. J Ultrasound Med 2004;23:1517–20.
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18. Zalel Y, Gamzu R, Weiss Y, et al. Role of color Doppler imaging in diagnosing and managing pregnancies complicated by placental chorioangioma. J Clin Ultrasound 2002;30:264–9. 19. Quintero RA, Reich H, Romero R, et al. In utero endoscopic devascularization of a large chorioangioma. Ultrasound Obstet Gynecol 1996;8:48–52. 20. Kriplani A, Abbi M, Banerjee N, et al. Indomethacin therapy in the treatment of polyhydramnios due to placental chorioangioma. J Obstet Gynaecol Res 2001;27:245–8. 21. Lau TK, Leung TY, Yu SC, et al. Prenatal treatment of chorioangioma by microcoil embolisation. BJOG 2003;110:70–3.
ORIGINAL ARTICLE
Placenta chorioangioma: a rare case and systematic review of literature Bassel H. Al Wattar1, Sarah C. Hillman1,2, Tamas Marton3, Katharine Foster4, and Mark D. Kilby1,2
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1
Fetal Medicine Centre, Birmingham Women’s Foundation Trust, Birmingham, UK, 2Centre for Women’s & Children’s Health, The School of Clinical and Experimental Medicine, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham, UK, 3Department of Perinatal Pathology, Birmingham Women’s Foundation Trust, Birmingham, UK, and 4Department of Pediatric Radiology, Birmingham Children’s Hospital, Birmingham, UK Abstract
Keywords
Objectives: Placental chorioangioma is a relatively rare condition that often results in serious prenatal complications and adverse pregnancy outcome. We report a case of a large chorioangioma that was prenatally diagnosed at 23 weeks with polyhydramnios and fetal anemia. With prenatal monitoring, transplacental therapy with a COX-2 inhibitor and intrauterine transfusion, the pregnancy resulted in the live birth at 30 weeks. Due to the paucity of evidence relating to the management protocols in cases of placental chorioangiomas, we have conducted a systematic review of the literature. Methods: All reported cases in the English language were captured using the electronic databases. Bibliographies of relevant articles were manually searched. Results: Sixty-four articles were included reporting 112 cases of placental chorioangioma. In 79, there was no prenatal treatment and in 33 there was in-utero treatment. A systematic comparison of antenatal complications and pregnancy outcomes was performed. No strong conclusion could be made due to the low number and quality of the reported cases. Conclusion: Placenta chorioangioma represents a challenge with its potentially serious complications adversely affecting pregnancy outcome. An international registry of pregnancies with this rare complication and documentation of pregnancy outcomes will improve the evidence base for prospective management.
Choriangioma, colour Doppler, intrauterine treatment, placenta, systematic review, tumor, ultrasound
Introduction Placental chorioangioma is the most frequent nontrophoblastic benign tumor of the placenta, reported to be present in about 1% of placentas examined by microscopy. However clinically evident, so-called ‘‘Giant’’ tumors are less common with an estimated incidence of between 1:3500 and 1:9000 births [1]. While the majority of tumors maybe asymptomatic in pregnancy (particularly when 54 cm), a significant proportion are reported as being associated with a number of serious antenatal complications such as fetal anemia, hydrops fetalis, polyhydramnios, antepartum hemorrhage, preterm labor and birth, intrauterine fetal growth restriction (IUGR) and increased perinatal mortality rates [2]. Early antenatal diagnosis, assessment and the possibility of intrauterine treatment could play a vital role in improving the pregnancy outcome. While different treatment methodologies have been reported and systematic reviews of the literature performed, absolute numbers remain small and there is no
Address for correspondence: Professor Mark D. Kilby, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK. Tel: 0121 627 2778. Fax: 0121 623 6875. E-mail: [email protected]
History Revised 30 April 2013 Accepted 18 September 2013 Published online 17 October 2013
strong evidence to support superiority of any single treatment [3,4] in terms of improving pregnancy outcome. We report a prenatally detected case of a large placental chorioangioma highlighting the importance of close surveillance, individualized pregnancy assessment to tailor therapy and early intervention.
Case report Mrs HM was a 26-year-old finance officer referred from her local district general hospital at 23 weeks and 4 days. She had a pre-pregnancy weight of 47.7 kg, a height of 157.5 cm, giving her a body mass index of 19.2. Her blood group was A Rhesus positive. She had a previous uncomplicated pregnancy in 2010 when she gave birth to a term baby weighing 3.6 kg. After referral, a detailed ultrasound scan at the tertiary Fetal Medicine Centre at Birmingham Women’s Foundation Trust, United Kingdom demonstrated an appropriately grown fetus (estimated fetal weight 536 g) with no fetal abnormality. The amniotic fluid volume was increased with a maximum pool depth of 7 cm. The placenta was relatively homogenous but a discrete, well circumscribed mass measuring 7 4 3 cm, adjacent to the umbilical cord insertion, that had the appearances of a placental Chorioangioma was noted (Figure 1). Colour flow Doppler demonstrated several large
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Figure 1. The placental chorioangioma on ultrasound.
‘‘vessels’’ running from the placental umbilical cord insertion and the tumor. Fetal Doppler waveforms demonstrated that the peripheral and intracardiac arterial and venous velocities were normal, with no evidence of fetal anemia and at that stage no evidence of cardiodynamic dysfunction. An oral glucose tolerance test excluded glucose intolerance and maternal serology for cytomegalovirus and toxoplasmosis demonstrated no abnormality. Serial ultrasound scans at weekly intervals were performed. At 25 weeks and 2 days, the liquor volume was noted to have increased significantly to a maximum pool depth of 10 cm. Again, Doppler assessment of the Ductus Venosus waveform demonstrated positive flow during atrial contraction and the umbilical artery Doppler velocity showed positive end diastolic flow. The middle cerebral artery peak systolic velocity was within normal limits for gestation. Maternal blood pressure remained normal at 120/80 mm/Hg and there was no proteinuria on urinalysis. The patient was started on Sulindac (a COX-2 inhibitor) at a dose of 200 mg twice daily orally. A fetal MRI confirmed the presence of a ‘‘well-defined lesion of homogenous signal in the caudal aspect of the placenta, close to the placental umbilical cord insertion’’ (Figure 2). This placental lesion measured 60 60 43 mm and appears to have a prominent vessel at its inferior aspect extending through it to the insertion of the umbilical vessels (within a centimeter of the tumor). It contained areas of ‘‘high T1 signal suggesting some hemorrhage within the lesion’’. The lesion also demonstrates restricted diffusion suggesting ‘‘high cellularity’’. With continuing maternal Sulindac therapy and regular review, the maximum pool depth of liquor decreased to 7 cm and this along with fetal biometry and peripheral and intracardiac arterial venous Doppler measurements were measured at weekly intervals and remained within normal limits for gestation. At 26 weeks of gestation a maternal course of prophylactic Betamethasone was given. At 27 weeks and 5 days, the maximum pool depth of amniotic fluid had decreased to 5 cm and therefore the Sulindac was discontinued. The patient remained normotensive. At 28 weeks and 2 days the patient was rescanned. The fetus had an
Figure 2. A (FIESTA) MRI section of the placental chorioangioma.
estimated fetal weight of 963 g and was below the 10th centile on customized growth charts. The maximum pool depth of liquor volume remained at 6 cm. However, the middle cerebral artery peak systolic velocity had increased and was elevated at 72 cm per second (41.5 MoM). The Ductus Venosus waveform demonstrated an elevated PVIV but there was positive flow during atrial contraction. There were also positive end diastolic velocities on umbilical artery Doppler insonation. The patient was rescanned 48 h after this and in addition to an elevated middle cerebral artery peak systolic velocity (greater than 1.5 multiples of the median) a small pericardial effusion had developed. The liquor volume had also increased so that the maximum pool depth was 7 cm and therefore maternal Sulindac therapy was reintroduced at a dose of 200 mg twice daily orally. A maternal Kleihauer test demonstrated no evidence of significant transplacental hemorrhage. Because of the associated risks of fetal anemia and placental chorioangioma, donor erythrocyte packed cells (irradiated and leuco-depleted) were prepared and percutaneous fetal blood sampling performed by cordocentesis of the placental cord root. The fetal hemoglobin was 6.3 g/dl (55 standard deviations from the mean for gestation) and the fetal platelet count was 435 109/L with a reticulocyte count of 12%. Transfusion of 50 ml of 80% hematocrit red packed cells was given to increase the fetal hemoglobin to 12.6 g/dl. Post-transfusion, a further fetal MRI scan was performed and again demonstrated a mass arising from the placenta at the site of the umbilical cord insertion. This had increased in size, measuring 8 7 5.8 cm. At 30 weeks and 2 days, a repeat ultrasound scan demonstrated the complete resolution of the pericardial effusion but a small rim of abdominal ascites. The fetus remained growth restricted but the umbilical artery Doppler velocimetry was within normal limits and the ductus venosus waveform showed positive flow during atrial contraction. A further course of maternal Betamethasone was given.
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Search methodology Our systematic review followed a prospective protocol developed using widely recommended and comprehensive methodology [9].
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Data sources
Figure 3. Photo of the placenta with the chorioangioma post-delivery.
A search strategy was developed based on existing advice for prevalence searches [10]. All the reported cases of placental chorioangiomas in English language were captured using the electronic databases MEDLINE (1966–Dec 2012), Embase (1980–Dec 2012), Cochrane Library (1999–Dec 2012). Bibliographies of relevant articles were manually searched to identify papers not captured by electronic searches. Eligibility criteria for selecting studies
A non-stressed cardiotocograph (CRT) demonstrated a fetal heart rate of 165 beats per minute with a short-term FHR variation measured at 510 ms. Because of fetal growth restriction, a rim of ascites and the reduced short-term variability on the CTG multidisciplinary discussion with our neonatal pediatric colleagues occurred. After this it was decided to deliver this fetus by emergency cesarean section. A live born baby girl weighing 1455 g was delivered. She had an Apgar score of 8 at 1 min and 10 at 5 min. The placenta was sent for histology (Figure 3). Macroscopic examination revealed a 16 13 3 cm placenta weighing 478 g with a pale, brown and homogenous tumor measuring 9 7 4 cm. Histological examination confirmed that the tumor is chorioangioma with signs of necrosis and dystrophic calcifications. The tissue show mostly capillary vascular proliferation with fibrotic connective tissue in between. Over the preceding 3 weeks the baby continued to gain weight and was discharged back to the local district general hospital for special care support. The baby continues to thrive and is alive and well. Systematic review of evidence for treatment of placental chorioangioma While the incidence of placental chorioangiomas is relatively low, its diagnosis and management represent a challenge due to its progression to antenatal complications and the increased risk of a poor pregnancy outcome. Early specialist scanning is important in managing placental chorioangiomas allowing early and prompt management of cases [5]. In our case, the patient had intensive and close surveillance with advanced scanning techniques that allowed early management with intrauterine treatments to prolong gestation and attempt to improve the fetal outcome. There have been several contemporary reviews of the literature examining the treatment in this potentially morbid condition [4,6]. These literature reviews highlight the nature of the small cohort studies available to give evidence base to these treatments and the heterogeneity of treatment choices. We performed a systematic review of the available literature which both updates available literature reviews and also uses methodology described according to STROBE and MOOSE criteria [7,8].
All reported cases were included and only opinion articles were excluded. Figure 4 shows the process of study selection. Reference lists were hand searched for relevant articles for inclusion. Inclusion and exclusion of papers was performed by two reviewers (B. H. W. and S. H.), any differences were resolved by a third reviewer (M. D. K.). Quality assessment and data synthesis STROBE was used to generate quality assessment of primary studies included [7] (Figure 5). Data were extracted into Excel tables and statistical analysis was performed using Fisher’s exact test as further described in the results.
Results Sixty-four articles were included in the systematic review reporting 112 cases of prenatally diagnosed placental chorioangioma. Of these, 79 did not have any treatment and 33 had prenatal interventions. From the literature, the mean gestational age at diagnosis was 28.5 weeks (range 16–40 weeks) and mean gestational age at delivery was 33.7 years (range 19–40 years). The mean size of the reported tumor was 60 mm (at the largest diameter) (range 20–200 mm). Comparison between prenatal treatment and non-treatment group A comparison of antenatal complications and outcomes between the treatment versus non-treatment group is highlighted in Table 1. The disease related antenatal complication rate (Fishers exact test, p ¼ 0.0004) appears to be higher in the treated group (prior to treatment) compared to the non-treated group. This was likely to be secondary to case selection, with those pregnancies deemed to be at risk being those in which invasive treatment was advocated. In addition, though, invasive treatment will carry a risk of iatrogenic fetal morbidity and mortality. All pregnancies resulting in live babies were considered to have good outcome. The complications of IUD, early neonatal death and admission to NICU were reported separately (Table 1). There was no difference in pregnancy outcome between treated and non-treated groups (Fishers exact test comparing good outcome of pregnancy, p ¼ 0.82).
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Figure 4. Process from initial search to final inclusion for systematic review of cases of placental chorioangioma.
Figure 5. Quality assessment of included paper using the STROBE checklist.
This could suggest that overall treatment/intervention may improve the outcome (as this group had more complications), but that the numbers are two small to draw any definite conclusions.
Comparison between specific treatment modalities The frequency of different treatment methods used and reported in the literature is demonstrated in Table 2.
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Table 1. Comparison of complications and outcomes between the treatment and non-treatment groups.
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Treatment group (need %)
Non-treatment group (need %)
p Value 1.0000 0.0004 0.0002 0.0004 1.0000 0.0015 0.5546 0.1392
MRI performed for diagnosis Antenatal complications Polyhydramnios Sings of hydrops IUGR Fetal anemia Placental abruption Pre term delivery
0/33 33/33 26/33 20/33 5/33 10/33 0/33 24/33
2/79 58/79 31/79 19/79 11/79 5/79 3/79 45/79
Admission to NU
Not reported 11 No 13 Yes 9
Not reported 21 No 39 Yes 19
Fetal outcome
Died 5/33 Good 23/33 Not reported 1/33 Stillbirth 4/33
Died 9/79 Good 57/79 Not reported 2/79 Stillbirth 11/79
1600 g ELSCS ¼ 6/33 EMLSCS ¼ 3/33 IOL ¼ 3/33 Not reported ¼ 1/33 NVD ¼ 20/33 TOP ¼ 0/33
1592 g ELSCS ¼ 7/79 EMLSCS ¼ 17/79 IOL ¼ 5/79 Not reported ¼ 0/79 NVD ¼ 47/79 TOP ¼ 3/79
Average birth weight MOD
0.5494 0.8210 1.0000
IUGR, intrauterine growth restriction; NU, neoonatal unit; MOD, mode of delivery; ELSCS, elective lower segment caesarean section; EMLSCS, emergency lower segment caesarean section; IOL, induction of labour; NVD, normal vaginal delivery; TOP, termination of pregnancy. Table 2. The frequency of treatment modalities in reported cases. Treatment mode Amnioreduction IUT Digoxin Laser ablation Alcohol injection ablation Bipolar coagulation Radiofrequency ablation Surgical clip application Surgical ligation Embolization
Frequency of cases 10 6 5 8 4 5 2 1 1 3
The pooled data set was too small to draw meaningful and significant conclusions in favour of one treatment modality over another. A brief narrative review of each treatment case is described in Table 3. The number of cases reported in the literature before the year 2000 was 54 with 11 cases treated (20.3%). This is in comparison to 59 cases reported after the year 2000 with 22 cases treated (37.2%).
Discussion This critical appraisal and systematic review of the literature complements those previously performed and highlights that prenatally diagnosed large placental chorioangioma are associated with a high incidence of antenatal complications. This highlights the importance of early diagnosis, individualized assessment and the consideration of in-utero management in such cases. Presently ultrasound and to a much lesser extent, in-utero magnetic resonance imaging (MRI), are the options of choice for imaging the placenta [11].
Colour flow and power-Doppler have made diagnosis more specific, have allowed the vascularity of the tumor to be assessed and may also allow the detection of angiomatous cellular and degenerative change [12]. Colour Doppler can be further used to visualize a discrete ‘‘feeding vessel’’, with consideration of vascular-occlusive therapy such as injection of sclerosing agents or fetoscopic laser ablation [4,13,14]. Successful prenatal intervention may be primarily achieved in those cases in which the chorioangioma is located away from the umbilical cord insertion site and by ‘‘Doppler mapping’’ noting that the circulation is not directly dependent on the umbilical cord. Peripheral and intrafetal arterial and venous Doppler imaging is also important in observing the response to treatment [11]. In our case, the fetus demonstrated no objective intracardiac findings of dysfunction and the very close proximity of the giant chorioangioma to the cord insertion gave cause for concern that feeding vessels may be multiple and large in size, making endoscopic laser coagulation more difficult and in all likelihood associated with complications such as vessel bleeding. Placental MRI has recently been reported as being used as an adjunct to ultrasound placental imaging [15]. This modality is safe in pregnancy, offers information about the maternal anatomy, the placental site and it has an ability to differentiate between different placental pathologies by Tweighting of the image. It may offer additional information to the clinician, guiding the management of such cases [11]. In our case study, the use of MRI offered accurate information about the nature of the placental mass, its size and position. From this perspective, it added little to the objective diagnosis but comments on T1/T0 weighing and cellularity were of interest and may be able to give information on differentiation between chorioangiomas and
Year of publication
2012
1998
2007
2003
2007
2006
1999
2003
2000
2000
2000
2003
2005
Author
Babic
Bashiri
Bermudez
Bhide
Deren
Esscribano
Haak
Hamill
Jauniaux
Jauniaux
Jauniaux
Kin Lau
Kin Lau
Polyhydramnios at 28 weeks. Preterm labour at 36 weeks. Polyhydramnios at 29 weeks. Preterm labour at 34 weeks. Polyhydramnios at 26 weeks. Oligohydramnios, MPD 3.7 cm þ fetal cardiomegaly þ fetal anemia at 24 weeks. Preterm labour at 29 þ 6 weeks. APH at 24 weeks, hydropic fetus þ generalized skin oedema þ bilateral pleural effusion þ pericardial effusion þ placentomegaly þ cardiomegaly þ polyhydramnios (AFI ¼ 21)
30 30 30 mm
200 180 170 mm.
100 80 60 mm
40 50 50 mm
Embolization with 1.5 mL of enbucrilate at 24 þ 2 weeks.
Amnioreduction at 26 weeks, repeated at 30 weeks. Intrauterine transfusion at 24 weeks and embolization intrauterine transfusion repeated at 27, 28 and 29 weeks.
Amnioreduction at 29 weeks
Intrauterine transfusion with 60 mL of Onegative blood at 25 weeks. Amnioreduction at 28 weeks
IUT with 100 ml of packed red cells.
IUT performed with 60 ml RBC at 16 weeks, Polyhydramnios þ pericardial effusion þ elevated MCA Ps persisted, alcohol injection into the tumor twice at 24 and 25th week. IUT at 25 weeks.
LSCS for breech presentation at 39 weeks, Female infant 3270 g good fetal outcome. Pre term at 32 weeks, NVD of female baby 2957 g, admitted to NNU for prematurity þ had about 25 small cutaneous hemangiomas spread over her body. Ultrasound examination of the heart showed ventricular hypertrophy. Discharged after 27 days. Induction of labour at 36 þ 4. Live baby, good outcome. Spontaneous Live baby of 3120 g. vaginal delivery at 36 weeks. Good outcome. Spontaneous Live baby of 2220 g. vaginal delivery at 34 weeks. Good outcome. Spontaneous Live baby of 3140 g. vaginal delivery at 38 weeks. Good outcome. An emergency classical caesarean section at 29 þ 6 for fetal malpresentation, a 1.185 kg baby was delivered. NND day 2 of life. SROM þ preterm at 26 weeks, breech position, emergency LSCS. baby girl weighed 845 g. Good outcome.
Live female delivered by elective lower segment caesarean at 32 weeks. Admitted to NNU for 3 weeks. Good outcome. Pre-term labour at 28 weeks, NVD with female infant of 1330 g, admitted to NNU for surfactant treatment. Discharged after 15 days.
IUD at 26 weeks.
YAG Laser ablation þ IUT þ amnioreduction at 24 weeks. IUT was repeated at 25 weeks. Interstitial laser at 24 weeks, repeated at 26 weeks.
Live male of 995 g. NND at? weeks
Amnioreduction at 24 weeks.
Postnatal outcome live female baby of 1.6 kg delivered by elective Caesarean section at 30 þ 4. Admitted to the NNU for 42 days. Good outcome.
Treatment performed Amnioreduction þ percutaneous embolization of the tumor by injecting enbucrilate (Histoacryl; n-butyl-2-cyanoacrylate liquid adhesive glue) Intrauterine transfusion with 50 mL of O-negative blood.
Placenta chorioangioma
20 20 30 mm
Fetal anemia at 25 weeks
60 64 45 mm
Mild cardiomegaly þ moderate/severe anemia at 25 weeks. Preterm @ 30 weeks þ polyhydramnios, þ Cardiomegalyþ hepatosplenom galy þ fetal anemia.
Polyhydramnios þ cardiomegaly þ pericardial perfusion þ dilatation of the hepatic vein suggesting heart failure þ fetal anemia at 16 weeks.
53 45 44 mm
53 48 61 mm
71 81 45 mm
72 83 mm
Antenatal complications Polyhydramnios at 22 weeks (MPD ¼ 13 cm). 30 weeks and 2 days of gestation, an ultrasound detected poor fetal right ventricular contractility with enlarged thick ventricular walls and mild pericardial effusion Polyhydramnios at 22 weeks. Preterm labour at 27 weeks Polyhydramnios, (MPD 12 cm) þ scalp edema and Ascites þ reversed flow in the ductus venosus þ fetal anemia at 24 weeks. Mild cardiomegaly at 23 weeks with hyperdynamic Circulation. IUGR at 26 weeks.
42 56 58 mm
Size of placental chorioangioma
Table 3. Brief summary of treated cases.
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1999
2005 1996
2003
2003
2009
2009
2009
1996
2002
2012
2002
2002
2002
2002
Nicolini
Quarello Quintero
Sepulveda
Sepulveda
Sepulveda
Sepulveda
Sepulveda
Wang
Wanapirak
Yen Lim
Zalel
Zalel
Zalel
Zalel
Polyhydramnios at 23 weeks. Fetal scalp oedema þ pericardial effusion þ Pleural effusion þ normal EDF in MCA at 24 weeks. Severe polyhydramnios at 26 weeks Polyhydramnios, hydrops, cardiac failure at 23 weeks. None.
38 34 44 mm 85 mm
75 56 mm
40 mm
70 mm
50 mm
130 mm
Mean of 83 mm
2 encapsulated masses: 1st 60 mm, 2nd 40 mm.
110 65 30 mm
Hydrops fetalis at 25 weeks.
Polyhydramnios at 21 weeks. Pre term at 26 weeks.
Polyhydramnios, pericardial effusion, cardiomegaly at 28 weeks. Polyhydramnios, hydrops fetalis at 29 weeks.
Polyhydramnios þ cardiomegaly þ pleural effusion þ ascites þ oedema of scalp at 24 weeks. Preterm labour at 25 weeks. Polyhydramnios þ signs of hydrops fetalis þ cardiomegaly þ minimal pericardial effusion þ mild ascites and a dilated intra-abdominal umbilical vein (8 mm) þ absent end diastolic flow at 27 weeks. Pre term at 32 weeks. 8 Cases diagnosed, 6 had polyhydramnios, 3 had non-immune hydrops and 5 had high cardiac output state.
Polyhydramnios with MPD ¼ 12 cm, short cervix of 22 mm with funnelling þ fetal anemia at 20 weeks. Pre term Labour at 28 weeks. Severe polyhydramnios and fetal hydrops at 20 weeks.
Polyhydramnios þ fetal anaemia at 22 weeks.
50 45 40 mm
68 60 mm
Polyhydramnios þ fetal anaemia at 25 weeks.
60 35 30 mm
Digoxin.
Amniocentesis þ digoxin.
Indometacin þ digoxin
Post-operatively, 80% survival rate, hydrops resolved in 2 of 2, cardiac output normalized in 4 of 4. All were live born at mean gestational age of 35.4 weeks. Five patients had fetoscopic devascularization. mean gestational age of 23.9 weeks. Bipolar coagulation (n 1), combination of bipolar and diode laser (n 2), bipolar and radiofrequency ablation (n 1), and surgical clip application (n 1). Digoxin.
Spontaneous vaginal delivery at 38 weeks. Good outcome. Premature rupture of membrane þ Spontaneous vaginal delivery at 26 weeks. Spontaneous vaginal delivery at 37 weeks.
Fetal demise at 33 weeks.
spontaneous vaginal delivery 32 weeks, female baby of 1360 g. Good outcome.
NVD at 25 weeks, died at 54 days.
Fetal demise at 29 weeks.
Emergency caesarean section 37 weeks for previous section, 3460 g female baby, good outcome. Emergency caesarean section 1150 g female baby delivered Died at 1 year of age due to an episode of acute renal insufficiency.
Spontaneous vaginal delivery at term. Good outcome. Fetal demise at 26 weeks.
Spontaneous vaginal delivery. Good outcome. Spontaneous vaginal delivery. Good outcome. LSCS at 39 weeks for breech, good out come IUD 3 days after treatment.
Alcohol ablation at 27 weeks.
Combined sonographic- and endoscopic guided intra-tumoral interstitial laser ablation at 28 weeks. Amniocentesis for karyotyping þ Digoxin given to mother at 24 weeks.
Intrauterine transfusion þ endoscopic laser coagulation.
Endoscopic laser coagulation þ amnioreduction at 24 weeks
Alcohol injection at 26 weeks.
Alcohol injection at 24 weeks. Repeated at 25 weeks. Laser ablation þ Amnioreduction. Ligation of feeding vessel to chorioangioma with 3-0 vicryl. þ bipolar coagulation to the rest of the feeding vessels. Amnioreduction at 27 weeks
Alcohol injection at 27 weeks.
B. H. Al Wattar et al.
A number of these cases have been reported previously in a number of literature reviews (2;4;21).
1999
Nicolini
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other placental masses such as haematoma (avascular), subchorionic fibrin (avascular), partial mole, hydropic degeneration, degenerating fibroid or placental teratoma [9]. However in our systematic review of the literature, the use of prenatal MRI, despite its non-invasive character was restricted to two cases and probably reflects clinician scepticism that this imaging modality adds important information. There is little consensus in the literature about the association between the chorioangioma size and its clinical manifestations. While many authors considered placental chorioangiomas to be clinically significant when larger than 4 cm (4;12) others suggested a ‘‘cut off’’ of 5 cm [16–18]. This systematic review noted that in 99 of the 112 cases reported the size of the chorioangioma was documented. In nine reported cases (9/99; 9.0%), the placental chorioangiomas was less than 4 cm. Four of these ‘‘small tumors’’ (4/9; 44%) had co-exiting fetal complications, but all had a good perinatal outcome. When the placental tumor was reported as measuring between 4 and 5 cm (12/99; 12.2%), all had perinatal complications and in three this was associated with a stillborn baby (25%). While in the 78 cases the ‘‘tumor’’ was reported to be 45 cm (78/99; 78.8%). In this cohort, there was with a reported fetal and perinatal mortality of 28.2% (13 fetal deaths and 9 stillbirths). Anecdotal descriptions, within relatively small case cohort studies, of invasive, in-utero treatment have been described. One of the earliest was by Quintero et al. in 1996 performing open surgical ligation of the feeding vessel to the chorioangioma. This intervention, perhaps unsurprisingly was associated with a poor outcome resulting in intrauterine death [19]. Subsequently, several types of in-utero, experimental treatment have been described with no strong evidence that one treatment modality is superior to any other. In our case study, we describe the use of the COX-2 inhibitor, Sulindac. This was utilized as there was associated polyhydramnios (with objective evidence of fetal cardiac compromise). The associated polyhydramnios has been linked to the tumor vasculature behaving as a vascular shunt predisposing to high cardiac output secondary to reduced fetal afterload. Indeed, there is evidence in the literature that such medical therapy may prolong gestation and therefore increased survival [20]. As already stated, the use of fetoscopic laser ablation of the ‘‘feeding vessel’’ to the large tumor was not performed in this case. The risks of the procedure in terms of vessel bleeding during laser ablation, due to the presence of multiple vessels and the close proximity of the tumor to the umbilical cord insertion were considered relatively contraindication (when the fetus was not demonstrating signs of cardiac dysfunction). The complication of fetal anemia has been described, in up to 15% of cases and has led to the use of serial middle cerebral artery peak systolic velocity measurements to screen for this complication [3]. In our case, intravascular, in-utero transfusion was the only invasive therapy used. Our systematic review of the literature, did not conclusively demonstrate the benefit of treatment over conservative management in improving the fetal and neonatal mortality. However, the numbers in this review are relatively small and
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bias of treatment in the most compromised babies is likely to be a confounding factor. Other outcomes such as neonatal morbidity need for emergency caesarean sections, resolution of polyhydramnios and hydrops were difficult to be analyzed due to the small number of reported cases. Prenatal treatment may be classified as (a) supportive (i.e. intrauterine transfusion, amnioreduction or by using transplacental pharmacotherapy) and (b) definitive treatment (i.e. surgical ligation/clipping, fetoscopic laser ablation, embolization, alcohol injection and radiofrequency ablation). Small number of cases, operator bias and low-quality information described in some papers (due to detailing of techniques) mean that no conclusive proof of benefit can be demonstrated. However, it is likely that therapy is only contemplated when there are ultrasound features of fetal compromise and the gestation is non-viable. These data indicate the need for an international register to document management in such cases and accurately record complications of therapy and perinatal outcome.
Declaration of interest All authors report no conflicts of interests. The authors alone are responsible for the content and writing of this article.
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DOI: 10.3109/14767058.2013.847424
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