Chorioangioma of the placenta associated with benign multiple neonatal hemangiomatosis

Abstract

Chorioangioma is one of the most frequent benign, non-trophoblastic tumors of the placenta, and occurs in 1% of all pregnancies (mostly in older pregnant women, multiparas and in pregnancies with female fetuses). The tumors are most commonly small, without any clinical symptoms and are found during postpartum inspection of placentas. When the tumor exceeds 4–5 cm in diameter, it can cause complications. It was reported that chorioangioma of the placenta can be associated with benign neonatal hemangiomas of the skin 1 and also with disseminated neonatal hemangiomatosis, which is a life-threatening disorder, involving multiple organs in newborns. The most informative diagnostic method of chorioangiomas is ultrasound (US) examination, combined with color Doppler flow 2. It can be difficult to differentiate chorioangiomas from bleeding and hematomas in the placenta by using only US scanning. Some authors suggest using MRI as another method of diagnosis 3. Chorioangioma of the placenta was also described in association with elevated maternal serum HCG in the second trimester of pregnancy 4. In our department, we observed a case of twin pregnancy with a suspicious area in the placenta under US examination, which was confirmed as chorioangioma of the placenta under postpartum microscopic examination. The size of the tumor was 8×6 cm; however, it did not cause any significant pregnancy complications. We, in addition, diagnosed multiple hemangiomas in one of the newborn twins. The patient was a healthy 37-year-old gravida 4, para 3, spontaneously pregnant with diamniotic, dichorionic twins, with 2 previous vaginal, uncomplicated deliveries. During early pregnancy, she was monitored with US examinations – US scanning with chorionic villus sampling examination in the 9th week and screening US in the 19th week of pregnancy. At this point, all the examinations were normal, including normally described placenta on the anterior uterine wall. In the 29th week, the control examination showed normal growth of the twins, adequate amniotic fluid (AF) volume, and normal pulsatility index. A mass, 6.5 cm in diameter, was found on the placenta's fetal surface, at the insertion point of the septum. The immediate differential diagnosis was made between a small biplacenta, a hematoma or, possibly, a dead third fetus. Afterward, the patient was monitored every 14 days. The pregnancy was uneventful until the 34th week, when she was admitted for frequent, painful contractions, upper right abdominal pain, and signs of effacement of cervix. There were no clinical or biochemical signs of preeclampsia. Ultrasound scanning of the described area in the placenta showed no changes in size and echodensity and no polyhydramnios. She was administered steroids for the enhancement of fetal lung maturation and was observed for premature birth. After 1 week, her condition stabilized and she was discharged for outpatient follow-up. At 38 full weeks, an uncomplicated cesarean section based on maternal request resulted in the birth of twins. Twin A: a boy at 2350 g, 48 cm, Apgar score 10/1 min, 10/5 min, pH 7.21, sBE −2.9. Twin B: a girl at 2525 g, 49 cm, Apgar score 8/1 min, 10/5 min, pH 7.33, sBE −1.7. Twin B had a small hemangioma at the right nostril (Figure 1). Small hemangioma of the nostril in a newborn. The macroscopic examination of the placenta showed two small tumors located in the central part, and one large tumor measuring 8×6 cm, located superficially on the fetal side of the placenta, at the septal insertion. The microscopic examination showed placental tissue with normal villi chorii and three tumors with mixed fibrous/myxomatoid stroma containing scant, benign stromal cells and normally distributed vessels. Intermingled were large, rounded areas of connective tissue with many, mostly small, vessels lined by normal endothelial cells. Proliferation of the trophoblast cells surrounded the tumors in focal areas. Minor variations in nuclear size were observed in these cells and proliferation marker Mib-1 showed an increased positive reaction. The findings were consistent with chorioangioma, which was the final diagnosis, despite the focal proliferation of the trophoblast with a slight degree of nuclear atypia. Similar results were published by Khong 5 who examined 23 chorioangiomas and showed proliferation of the trophoblast in 65% of patients, which all had benign clinical course. The patient was followed until serum-HCG level was zero. During the first week of life, twin B developed multiple hemangiomas on the skin, but remained in good condition (Figure 2). Twin A's condition was also good, without visible hemangiomas. In order to exclude disseminated neonatal hemangiomatosis, twin B was followed up clinically and with US examination of the abdomen and the lungs. There were no signs of hemangiomas in the internal organs. It was concluded that the condition of the newborn was a benign hemangiomatosis of the skin, which, after an initial rapid increase of hemangiomas in number and size, is characterized by a spontaneous regression during the first year of life. Already at the checkup at the age of 4 months, there remained only one hemangioma in the pampers area and the size of the primary lesion at the right nostril was substantially decreased. Multiple hemangiomas on the skin in a newborn. With an incidence of 1% of all pregnancies, chorioangioma is not a rare phenomenon. It is well shown that chorioangiomas bigger than 4–5 cm in diameter frequently cause serious pregnancy complications, and can also increase neonatal morbidity and mortality, because of their causal connection with hemangiomas in children. This connection has been demonstrated by immunohistochemical studies 6, which showed unique expression of tissue-specific markers both in infantile hemangiomas and in placental vessels, but not in normal skin vasculature or other benign vascular tumors, similar to hemangiomas. This similarity between the vascular structures in the placenta and neonatal hemangiomas suggests a common cellular origin, although hemangiomas in newborns do not contain trophoblastic cells and are not classified as placental tissue 6. Angiogenesis in the placenta is regulated by vascular endothelial and placental growth factors as well as soluble inhibitors of angiogenesis, all of which are produced by placenta itself and have been found both in maternal serum and in AF 7. Loss of placental regulation of angiogenesis after separation of placenta at birth can play certain role in unrestricted proliferation of embolized or aberrant cells of placental vascular phenotype, thus the development of hemangiomas in newborns. Chorioangioma should be kept in mind whenever a pregnant woman presents with one or more of the following complications – polyhydramnios, premature birth, preeclampsia, antenatal bleeding, fetal cardiomegaly, anemia, cardiac insufficiency, hepatomegaly, IUGR, and hydrops fetalis 1, 2, 4. It is considered that large chorioangiomas function as a peripheral arteriovenous shunt, which can be one of the pathogenetic mechanisms in the abovementioned conditions. It is important to diagnose asymptomatic tumors in order to closely monitor these pregnancies for possible complications. The condition is best diagnosed with US examination combined with color Doppler flow, which helps differentiate between chorioangiomas and other placental tumors or hematomas. Symptomatic chorioangiomas can be treated by delivery, if the gestational age permits it, or, in the case of some patients, therapeutic amniocentesis, intrauterine transfusion, alcohol injection in the tumor, or laser destruction. Newborns with skin hemangiomas should be followed up closely during the first 3–6 months in order to exclude disseminated neonatal hemangiomatosis, which is characterized by the involvement of three or more organ systems (most frequently the liver, the intestines, the lungs, and the brain), or at least the skin and the liver 8. Close follow-up is necessary, because this condition is associated with 60–90% mortality rate in the first months of life, usually because of high-output cardiac failure 9, consumption coagulopathy, and hemorrhage.