Non-immune hydrops fetalis associated with two umbilical cord hemangiomas and vascular malformation of the transverse mesocolon. Case report

Summary

Umbilical cord hemangioma is a rare tumor that can be associated with significant fetal and perinatal complications. Although usually described as a single anomaly, sometimes these tumors are reported in association with other vascular lesions. We report an unusual case of simultaneous occurrence of two umbilical cord hemangiomas and vascular malformation of the transverse mesocolon in a stillborn fetus with hydrops. To our knowledge, this is the first report of two simultaneously occurring umbilical cord hemangiomas. Moreover, presence of associated vascular malformation of transverse mesocolon could support the hypothesis of underlying predisposition to the development of vascular tumors.

Keywords:

hydrops fetalis – hemangioma – umbilical cord – stillbirth – vascular malformation – transverse mesocolon

The presence of hydrops fetalis generally portends a poor prognosis, with substantial risks of intrauterine fetal demise, preterm labor, and neonatal morbidity and mortality. Once this condition is identified, it is important to systematically perform the differential diagnosis. The majority of cases are non-immune in nature, and wide variety of causes are known to lead to non-immune hydrops fetalis (1-4). Umbilical cord lesions associated with vascular constriction and/or obstruction are considered to be the rare causes of hydrops fetalis (2,5,6).

Umbilical cord hemangiomas are benign vascular tumors usually presenting as a fusiform swelling within the cord with presence of an angiomatous nodule on cut surface (7-9). Although morphologically umbilical cord hemangiomas are very similar to the more common placental hemangiomas (chorangiomas), the frequency of the former lesion is much lower than that of placental hemangiomas (7-15). This is the first case we have seen in our practice, although hundreds of placentas are examined yearly in our institute.

Histologically, the tumor is composed of anastomosing vascular structures, lined by endothelium, and surrounded usually by a myxoid or mucoid stroma (7,8,12,13,16). The etiology of umbilical cord hemangiomas remains unclear. Previous studies reported no apparent association between fetal sex, maternal age, race, or gravidity, and development of cord hemangiomas (7,10,13). These tumors typically occur as an isolated anomaly, although they have been also described in asociation with other malformations, including skin and systemic hemangiomas (9,11,15,17).

Here we report an unusual case of two umbilical cord hemangiomas and associated vascular malformation of transverse mesocolon in a stillborn male fetus with hydrops.

CASE REPORT

A 34-year-old Asian woman, gravida 4, para 1, with a medical history of two missed abortions and one spontaneous full term delivery of a child diagnosed with DiGeorge syndrome, had a routine ultrasound scan at 22 weeks that showed polyhydramnios and hydrops fetalis. Moreover, ultrasound examination demonstrated a hyperechogenic mass within the umbilical cord measuring approximately 3 x 2 cm (Fig. 1). The mass was located near the fetal insertion of umbilical cord. No other abnormalities were detected. The fetal abdominal wall was intact. Hematogenous infections associated with non-immune hydrops fetalis as well as Rh isoimmunization were excluded. Amniocentesis was performed. Amniotic fluid cells showed normal 46, XY male karyotype. Levels of maternal serum alpha-fetoprotein were normal. At 28 weeks the woman felt decrease of fetal movements and saw her gynecologist. Ultrasound examination showed no fetal heartbeat. The woman was referred to the hospital and one day later she delivered a male fetus with no signs of life after medical induction with prostaglandins at 28+6 weeks of gestation.

The macerated fetus was 40 cm long and weighted 2560 g. The autopsy showed an excessive accumulation of serous fluid in the fetal tissues and body cavities. Bilateral pulmonary hypoplasia was present. In the transverse mesocolon there was found an edematous vascularized mass measuring approximately 4 cm in the largest dimension. Umbilical cord was 68 cm long. Approximately 1 cm from fetal insertion, there was an ovoid solid mass with smooth surface measuring 3 x 2 x 1.5 cm (Fig. 2). The cut surface of the lesion revealed a numerous blood-filled vascular channels (Fig. 3A). The Wharton’s jelly adjacent to the lesion was edematous. In the placental insertion site of the umbilical cord, there was surprisingly found another similar lesion measuring 1.1 x 1 x 1 cm, and consisting of multiple small vascular channels (Fig. 3B). Placenta was pale and enlarged, it weighted 450 g and measured 19 x 17 x 3 cm.

Histologically, both umbilical cord masses were composed of numerous small branching vessels proliferating in the background of myxoid stroma of Wharton’s jelly. Vascular channels were lined by flattened endothelium positive for CD31 and CD34 (Fig. 4A, 4B and 4C). The lesions fulfilled the pathological criteria of an umbilical cord hemangioma. Both hemangiomas were in the close contact with the wall of umbilical vein. Neither calcification, thrombosis nor osseous metaplasia were present. Examination of placenta showed chorionic villi with stromal edema and increased numbers of Hofbauer cells and changes consistent with intrauterine fetal demise, including intravascular karyorrhexis. Vascular malformation of the transverse mesocolon was composed of multiple dilated vascular structures of variable size and thickness of the wall (Fig. 5A and 5B). The lesion was not encapsulated but relatively well demarcated from surroundings.

DISCUSSION

Hydrops fetalis is estimated to occur in 1 per 3000 pregnancies and is traditionally defined as an abnormal accumulation of fluid in at least two fetal compartments, inluding ascites, pleural effusion, pericardial effusion, and skin edema (2,5,18). The majority of cases are non-immune in nature and wide variety of congenital infections, cardiovascular diseases, tumors, genetic causes, maternal diseases or placental and umbilical cord lesions are known to lead to non-immune hydrops fetalis (1-4). The main factors involved in the pathogenesis of fetal hydrops are severe fetal anemia, hypoproteinemia, fetal heart failure and interference with fetoplacental circulation impedance to venous return from placenta (5,19). Placental and umbilical cord lesions that have been associated with non-immune fetal hydrops include chorangiomas, umbilical vein thrombosis, torsion or true knots (1,5,6).

Large placental chorangiomas, measuring more than 5 cm, can act as a high volume arteriovenous shunts and lead to hydrops due to high cardiac output. The increased demand for cardiac output leads to cardiac failure, and corresponding edema. It is assumed that other vascular tumors and malformations can similarly cause non-immune hydrops fetalis (1,6). Umbilical cord lesions associated with umbilical vein constriction and/or obstruction lead to increase in hydrostatic pressure in umbilical vein proximal to obstruction. Initially, the umbilical venous partial obstruction could lead to increase in intravillous capillary pressure resulting in villous edema and subsequent fetal hypoxemia. Later, fetal cardiac function may be impaired because of increase in placental villous pressure. Collectively, it may give rise to fetal hydrops (19,20).

Umbilical cord tumors are rare findings. Only two true tumors of the cord are described: hemangioma and, more rarely, teratoma (7,8,10,13,21). Hemangioma of the umbilical cord is a benign vascular lesion of various size (7-14) usually located near the placental insertion of the cord (7,10,13). Histologically, the tumor is composed of multiple branching vessels surrounded usually by a loose myxoid connective tissue (7,8,12,13,16). Sometimes thrombi, calcifications or osseous metaplasia can be found within the tumor (7,8,10,12). The myxoid appearance has lead some authors to call this lesion angiomyxoma (7,11,22). Edema, myxoid and cystic changes of the Wharton’s jelly adjacent to the tumor are nearly constant findings (7-9,12,13,16,17,20). These changes are due to high permeability of angiomatous vessels placed in a gelatinous tissue (7,13). The tumor presumably arises from one or more of the major umbilical vessels or vitelline capillaries. Some authors hypothesize that umbilical cord hemangioma is a hamartoma rather than a true neoplasia and that it arises as a malformation of the primitive angiogenic mesenchyma of the developing cord (7,8,13,14,23). The etiology of the lesion remains unclear. The most frequent presentation of the tumor is that of isolated fetal anomaly, although it has been repeatedly described in asssociation with skin and visceral hemangiomas (9,11,15,17,24,25). A causal relationship has not been definitely established, but some authors suggest that there could be an underlying predisposition to vascular neoplasms (10,11). Moreover, umbilical cord hemangioma has also been reported in association with Klippel-Trenaunay-Weber syndrome, a condition characterized by a triad of findings: cutaneous hemangiomas, soft tissue and bone hypertrophy, and vascular malformations (26). On the other hand, the gastrointestinal and heart malformations (24), hypospadias (27), anencephaly (28) and limb deformities (29) reported in the literature are probably just random coincidences. Polyhydramnios and increased alpha-fetoprotein have been reported in some cases (10,12,15,29,30).

Although umbilical cord abnormalities can be detected through antenatal ultrasound scans, the definitive diagnosis commonly can not be made because of nonspecific findings. When the umbilical cord abnormalities are suspected, the differential diagnosis should include hematomas, varices, aneurysms, thrombosis, cystic lesions such as omphalomesenteric duct cyst or allantoic cyst, abdominal wall defects and last but not least tumors (10,31).

The possible clinical significance of the umbilical cord hemangioma remains obscure. Most authors report a potential risk of fetal and perinatal morbidity and mortality, especially due to premature delivery, heart failure, severe fetal hemorrhage, non-immune hydrops fetalis and intrauterine death (7,8,13,16,32). It is suggested that mechanical compression of umbilical vessels by a tumor or cord torsion are the most plausible reasons for impairment of umbilical circulation, which is considered as the predisposing factor for poor fetal outcome. In addition, there are several other theories relating to how cord hemangioma affects the umbilical circulation, including acting as a arteriovenous shunt. Progressive edema and cystic degeneration of Wharton’s jelly, very frequent findings associated with umbilical cord hemangioma, could also contribute to vessel compression (12,20,23,30,33).

In our case, the compression of umbilical vessels, specifically vein, by two tumors at both insertion sites of the cord, seems to be the most probable cause of circulatory compromise which resulted first in hydrops fetalis and subsequently in fetal intrauterine death. To the best of our knowledge, this is the first report describing two simultaneously occurring hemangiomas of the umbilical cord. A PubMed search of the literature published since 1951 revealed no similar case. Moreover, the presence of an associated vascular malformation of transverse mesocolon could support the hypothesis of underlying predisposition to vascular neoplasms.

CONCLUSION

Despite its rarity, one should be familiar with existence and clinical significance of this tumor. Once identified prenatally, the mother should be counseled for possible fetal complications. If detected in the neonatal period, infants should be carefully examined with the knowledge that associated vascular lesions may be present.

ACKNOWLEDGEMENTS

This study was supported by the Ministry of Education, Youth and Sports grant SVV–2021-22 639.

CONFLICT OF INTEREST

The authors declare that there is no conflict of interest regarding the publication of this paper.

Correspondence address:

MUDr. Magdaléna Daumová, Ph.D.

Sikl’s Institute of Pathology, Faculty of Medicine and University

Hospital in Pilsen, Charles University

Edvarda Benese 1128/13, 305 99 Pilsen

Tel.: +420 377 402 089

e-mail: daumovam@fnplzen.cz