Multiple Chorangioma Following Long-Term Secondary Infertility: A Rare Case Report and Review of Pathologic Differential Diagnosis.

Chorangioma (placental hemangioma) is a benign non-trophoblastic neoplasm of the placenta. Small chorangiomas are usually asymptomatic, but the giant and multiple ones rarely have a favorable outcome. We report a case of 29 weeks of gestational age (after long-term secondary infertility) with premature labor pain and undiagnosed multiple chorangioma leading to hydrops fetalis and neonatal death. Here we report the clinicopathological features of our case and chorangioma in general, along with comparison of different vascular lesions of placenta in terms of incidence, risk factors, complications, histologic origin, macroscopic and light and electron microscopic features.

Introduction

Chorangioma (placental hemangioma) is a benign non-trophoblastic neoplasm of the placenta, having an incidence of 1% on gross pathological examination. Most placental chorangiomas are small and located entirely in placental substance, that is why they could be missed easily unless the placenta is systematically sliced after delivery.1,2 Small chorangiomas are usually asymptomatic, but the giant and multiple ones rarely have favorable outcome. So prenatal diagnosis would help to predict the pregnancy outcome and taking interventions if possible. We hereby present a case of 29 weeks of gestational age with undiagnosed multiple chorangioma and neonatal death.

Case Report

A woman aged 31, G2P0A1, at 29 weeks of gestation was admitted to the emergency center of Obstetrics and Gynecology department of Shiraz University of Medical Sciences, Iran, due to premature labor pain. Current pregnancy had occurred spontaneously after a long period of secondary infertility (12 years). There was a notable history of failed IUI (intra uterine insemination) 12 years ago. During this long time no study was done to evaluate the cause of infertility. She also had a history of appendectomy before marriage. Pelvic examination revealed active phase delivery and due to no beat-to-beat NST (non stress test), emergency cesarean section (c/s) was performed with the birth of a poor Apgar girl weighing 1250 g with gross features of hydrops fetalis. Unfortunately she had only one normal obstetric sonography which was done early in pregnancy. Additional follow up of the neonate showed dilated cardiomyopathy and she passed away after 14 days. The placenta which was sent for pathologic examination, weighed 450 g and placental disc measured 16 cm in greatest diameter and 2 cm in maximal thickness with membranous insertion of umbilical cord. Furthermore it revealed multiple well circumscribed creamy rubbery masses measuring from 0.2 to 4 cm at maternal surface (Figure 1). Microscopic examination of different nodules showed well demarcated lesions composed of numerous capillary sized vascular channels that were covered by trophoblastic layers (Figures 2–4).

Figure 1

Gross features of placenta show multiple well defined rubbery nodules located on the chorionic plate.

Figure 2

Microscopic examination of one nodule showing a well demarcated vascular lesion resembling capillary hemangioma (H&E × 10).

Figure 4

Numerous capillary sized vascular channels (H&E × 40).

The lesion is covered by a trophoblastic layer (H&E × 40).

Written informed consent has been provided by the patient for publication of this case report, including images. Our institutional approval is not required to publish the case details.

Discussion

With rare exception, vascular tumors are the only benign tumors of the placenta.3 Chorangioma and chorangiosis are two sides of a spectrum that pass through chorangiomatosis. They are lesions of capillary dysvasculogenesis with different clinical presentation and complications, however some overlapping features are always present (Table 1).

Table 1

Clinical Features of Different Vascular Lesions of Placenta

Lesion	Incidence	Gross Features	Origin	Risk Factors**	Complications**
Congestion	*	No distinct gross abnormality	*	*	No complication
Chorangiosis	Variable	No distinct gross abnormality	Terminal villi1	Pre-eclampsia, DM, drug ingestion, UTImultiple gestation,smoking6,7	IUGR, IUFD, fetal malformation, c/s
Chorangiomatosis	0.554	Heterogenous and less well defined lesions	Mature stem villi1	Pre-eclampsia, multiple gestation and prematurity4	IUGR8 Premature delivery
Chorangioma	1%1	Small solitary well defined nodule	Mature stem villi1	Women over 30 years, HTN, twin pregnancy, maternal smoking and living at high altitude8–10	Premature deliveryHeart failureFetal hydropsMHA, IUFD11
Atypical chorangioma	Very rare5	Solitary well defined nodule	Mature stem villi	Undetermined	Undetermined

Notes: *Not applicable. **There is some overlapping between different lesions.

Abbreviations: LPF, low power field; MHA, microangiopathic hemolytic anemia; DM, diabetes mellitus; HTN, hypertension; IUFD, intra uterine fetal death; IUGR, intra uterine growth retardation; MHA, microangiopathic hemolytic anemia.

Hypoxia may lead to excessive villous capillary growth and proliferative activity of connective tissue, probably mediated by vascular growth factors.6 That i̓s why chorangiomas tend to be in areas with hypoperfusion and chorangiosis is a secondary process involving a response of the placenta to fetal hypoxia.11 In our case previous abortion and IUI could be considered as the cause, since they can create hypoperfused areas in the uterus.

Chorangiomas are often seen as solitary nodules, mostly buldging from the fetal surface of the placenta or attached to the placental disc by a pedicle with a greater frequency in less perfused areas such as chorionic plate and placental margins.1,12

They are usually small and microscopic but multiple and larger ones have also been found with 26x20x12 cm size in the largest reported case.13

Grossly, chorangiomas are sharply circumscribed from the surrounding parenchyma. Usually there is a fleshy, congested, red/tan cut surface with occasional presence of myxoid, fibroma-like or degenerative changes.1

Microscopically, it shows a well-defined lesion arising from stem villi composed entirely of blood vessels within a cellular stroma and often surrounded by trophoblasts.1

Histologic variants include: capillary, cavernous, endotheliomatous, fibrosing and fibromatous, among these, capillary type is the most frequent histological type.14

Sometimes there is association of degenerative changes such as hemosiderin deposition, hyalinization and also calcification.1

The sonographic appearance of chorangioma is a well-defined predominantly hypoechoic mass. Color Doppler imaging can define the presence of a single feeding blood vessel with branching pattern and could contribute to rule out other uterine pathologies with similar sonographic appearances, such as placental hemorrhage, sub-chorionic hematoma, myoma, placental teratoma, and molar pregnancy. MRI could also be helpful in chorangioma management.12,13

The rate of occurrence rises in women over 30 years, presence of diabetes, hypertension, twin pregnancies (both monozygous and dizygous), maternal smoking and living at high altitude.8–10

While small chorangiomas are usually asymptomatic, the multiple and larger ones (greater than 4 cm), can induce significant effects on hemodynamic and circulatory processes of the fetus with overall mortality rate of 30%.15

More vascular and hypoechoic tumors are associated with higher incidence of pregnancy complications.16

Rare occurrence of recurrent chorangiomas poses the role of genetics in its creation. In the few published instances of recurrent chorangioma, the masses were always multiple or even numerous.17

Association with Beckwith-Wiedemann syndrome, placental mesenchymal dysplasia and concurrence of multiple chorangiomas with fetal hepatic hemangioendothelioma have been reported.18

As we know, pregnancies with the most serious complications often present in the late second trimester, at which time delivery is not an option. It seems that treatment with intrauterine transfusion could be a preventive intervention.12,19–21

Microscopically normal placental villi should contain no more than 5 vascular channels, even when the same vessel is present in more than one plane of section. Table 2 shows histological differences between different vascular lesions of placenta in examination using light and electron microscopy.

Table 2

Histological Differences Between Different Vascular Lesions of Placenta

Lesion	Light Microscopy	Electron Microscopy
Congestion	Prominent capillaries, but the vasculature is numerically normal22	No specific change
Chorangiosis	A diffuse process >10 capillaries in >10 terminal villi in at least 10 different non-infarcted areas in 3 LPF20All vessels have the same caliber8	Each capillary is surrounded by a distinct basement membraneLack of MSA-positive pericytes around the vesselsLack of lattice-like pattern of reticulin fiber1
Chorangiomatosis	Ill-defined proliferation of variable sized capillaries (concentrated in the center of villi) surrounded by circumferential layer of pericytes8	No distinct basement membraneBundles of reticulin fibers surround capillaries
Chorangioma	Well defined proliferation of capillary sized blood vessels and surface trophoblastic proliferation	No distinct basement membraneContinuous layer of MSA-positive pericytes around each vesselBundles of reticulin fibers will merge in the surrounding villous stroma in a lattice-like loose pattern1
Atypical Chorangioma	Similar to chorangioma plus increased cellularity, mitotic activity and areas of necrosis5	Similar to chorangioma plus mitosis and (or) necrosis

Congestion is sometimes confused with vascular tumors at first glance microscopically.

Chorangiomatosis in the focal variant is similar to chorangioma and in the diffuse multifocal form shares some features with chorangiosis.23

To our knowledge by far only rare cases of true multiple chorangiomas, like ours, have been reported and most cases which are reported as multiple chorangioma are just diffuse chorangiomatosis due to lack of well circumscribed nodules.

Conclusion

Vascular lesions of the placenta are in fact a spectrum of variable lesions with some common clinical and pathologic features and from chorangiosis to chorangioma the outcome is worse, especially in multiple and large lesions.