Prenatal diagnosis of rapidly involuting congenital hemangioma: a case report and review of the literature

Introduction

Congenital hemangioma (CH) is a rare benign vascular tumor, the true incidence of which is unknown. The main clinical difference with the more common infantile hemangioma is that they present as fully mature lesions at birth. In utero diagnosis of these lesions is rare. We present a case of a prenatally diagnosed congenital hemangioma of the forehead, later identified as a rapidly involuting congenital hemangioma (RICH). The lesion was first discovered on routine fetal morphology ultrasound assessment at 19 weeks’ gestation. The early diagnosis allowed close surveillance of the fetus and neonate and an observation of the natural course of this lesion. In contrast to some other case reports, the lesion caused no adverse fetal effect and no intervention was required.

Case report

A 36-year-old woman, in her third pregnancy presented at our specialist prenatal ultrasound department for routine fetal morphology scan at 19 weeks’ gestation.

Her two previous pregnancies were uneventful resulting in full-term vaginal deliveries of healthy neonates. All pregnancies were conceived naturally. There was no relevant personal or family history. Non-invasive pregnancy aneuploidy testing (NIPT) at 11 weeks resulted in low risks for the common trisomies.

At the time of the morphology ultrasound a small avascular nodule of around 14 × 7 × 7 mm (0.2 mL) was identified on the forehead, superior to the skull, as an isolated finding. Ultrasound review at 23 weeks revealed further growth of the lesion to 21 × 6 × 19 mm (1.3 mL) and visible internal vascularity with an arterial blood supply seemingly branching from the left supraorbital artery (Figure 1A). The peak velocity in the artery of 30 cm/s, demonstrated the fast-flowing character of the lesion (Figure 1B). The features were most suggestive of a congenital hemangioma (Figure 1C). As described in the context of vascular anomalies, we mapped the vessel density determined by the number of vessels per square centimeter (cm²) [1]. Based on this, lesions can be classified as low (<2 vessels per cm²), moderate (2–4 vessels per cm²) or high density (>5 vessels per cm²). The vessel density in this case never exceeded five vascular elements/cm².

Figure 1:

(A) Congenital hemangioma (white arrow) at 22 weeks 5 days GA; (B) fast-flow character of the lesion showing arterial blood supply arising from a left supraorbital artery; (C) tree-dimensional (3D) rendering of the congenital hemangioma (white arrow) at 22 weeks 5 days GA; (D) congenital hemangioma (white arrow) of 7.5 mL at 27 weeks’ GA.

Given the significant vascularity of this lesion, close ultrasound monitoring was instituted for early identification of incipient cardiac compromise and fetal hydrops. In the following weeks, the lesion continued to expand, measuring 25 × 16 × 22 mm (5 mL) at 24 weeks’ GA, 29 × 15 × 30 mm (7.5 mL) at 27 weeks GA (Figure 1D) and reaching a maximum in absolute size by 31 weeks when it measured 38 × 35 × 18 mm (14 mL). In order to appreciate the relative growth, we determined the mass/head circumference ratio at each visit, which demonstrated rapid growth initially, with growth velocity slowing after 31 weeks’ GA (Figure 2).

Figure 2:

Growth of the hemangioma from 19 to 35 weeks’ GA. Red: the absolute measurement in mL Blue: the mass volume to head circumference ratio in mL.

Magnetic resonance imaging at 26 weeks concurred with the diagnosis and identified the mass as confined to the dermis without bony involvement. Array comparative genomic hybridization following amniocentesis excluded all major copy number variations and confirmed a 46, XY genotype.

The tumor remained unchanged in appearance and size from 35 weeks’ GA until birth and no adverse fetal effects were identified. At 39 weeks’ GA, an elective cesarean section was performed, delivering a healthy baby boy of 2.97 kg. The erythematous hemangioma on the forehead was similar to the size estimated from the final ultrasound at 35 weeks’ GA. Postnatally the hemangioma showed a rapid decline in volume, supportive of it being a RICH, leaving some residual skin excess and discoloration at 4 months of age (Figure 3), which is likely to completely resolve by 14 months.

Figure 3:

(A) Congenital hemangioma (white arrow) immediately after birth (39 weeks’ GA); (B) significant reduction of the congenital hemangioma (white arrow) at 2 months of age; (C) congenital hemangioma (RICH) (white arrow) at 4 months of age showing some skin excess and mild skin coloration.

Discussion

Two main and a third overlapping sub-type of congenital hemangiomata can be distinguished; the rapidly involuting congenital hemangioma (RICH), the non-involuting congenital hemangioma (NICH) and the partially involuting congenital hemangioma (PICH). They are characterized as fast-flow lesions located in the dermal or subcutaneous layer. Their proliferative phase is completed in utero, presenting as fully grown tumors at birth, differentiating them from the more common infantile hemangiomata. Additionally, in contrast to the latter, they lack expression of glucose transporter protein-1 (GLUT-1) on the endothelial cells.

The prevalence is equally distributed amongst males and females.

The RICH sub-type typically presents as a round or oval-shaped, protuberant, purple, soft-tissue mass. The surface of the tumor is often telangiectatic with pale skin and pale halo. Central ulceration can be seen as a function of the natural involution course. Histologically they are formed by lobules of capillaries of various size and prominent endothelial cells. These lesions most often spontaneously disappear by 14 months of age and therefore do not require intervention. Surgical excision or vascular embolization may be necessary in the case of functional impairment, ulceration or bleeding, residual tumor after involution or in the rare event of hemodynamic deterioration. When involution is completed, skin excess and discoloration are commonly found as well as remaining telangiectasia.

On prenatal ultrasound, RICH can be recognized as an exophytic heterogenous tumor of variable size which tends to show a rapid growth in utero. It is characterized by lobules with small arteries and larger venous draining channels. Calcification may be present.

When occurring in the liver, RICH usually present as solitary, well-defined vascular tumors with large-caliber vessels. Rarely these lesions can lead to cardiac failure due to arteriovenous shunting, anemia, thrombocytopenia, coagulopathy, disseminated intravascular coagulation, hepatic failure and postnatal feeding disorders due to its mass effect. However, most often their course is uncomplicated, characterized by a spontaneous regression after birth. Medical treatment in an asymptomatic patient is controversial and is generally avoided.

The NICH sub-type exhibits some overlapping characteristics with the RICH sub-type. They present as a round or oval-shaped, purple tumor with coarse telangiectasis and a pale background. Large venous vessels can sometimes be seen in the deeper layers of the surrounding skin. Central ulceration is less common. Two subtypes have been described; the flatter ‘patch’ type and the ‘nodular/plaque’ type [2].

Similar to the RICH lesions, they present as mature tumors at birth, but in contrast to RICH, NICH lesions continue to evolve directly in proportion to the infant’s size. Surgical excision of the lesion is often performed but residual tumor and recurrence of NICH can occur [2].

NICH lesions are rarely identified on prenatal ultrasound as they typically cause only mild skin elevation. On histology they are characterized by small thin-walled vessels with a centrally positioned stellate vessel lined by hobnail endothelial cells. Arteriolobular and arteriovenous fistulae are often present [3].

Mulliken and colleagues [4] described 10 cases in their paper where the involution of the RICH ceased prematurely resulting in a residual NICH. They hypothesized that a NICH lesion could represent a later stage RICH lesion. Similar findings have been reported by Nasseri et al. [3]. They however acknowledged this phenomenon as a potential third variety, namely the PICH.

Uncommonly, complications can be encountered in cases of larger congenital hemangiomata.

Hemorrhage, either due to ulceration or trauma, may warrant early medical intervention. Nolan et al. [5] presented a case of life-threatening hemorrhage of an unsuspected RICH following a vaginal delivery. This underscores the importance of prenatal diagnosis of RICH, allowing appropriate decision-making regarding the mode of delivery. Although no formal recommendations are made, delivery by cesarean section should be considered, especially in case of larger RICH.

Ulceration of the lesion can be another cause of significant hemorrhage, even more so in case of RICH lesions [6], [7], due to the more superficial position of the vessels. Severe hemorrhage can be treated by tranexamic acid [6], embolization and/or surgical resection of the tumor. One case report described the successful use of transcutaneous in-situ sclerosis with tissue adhesive [7].

Several case reports have identified thrombocytopenia in association with RICH lesions in the postnatal period. Baselga et al. [8] published seven cases of large (>5 cm) RICH lesions, all presenting with transient thrombocytopenia and coagulopathy in the immediate postnatal period. Two patients underwent embolization, four received corticosteroids and one recovered without any treatment. No difference in recovery time was seen between the treated and untreated patients.

Weitz et al. [9], provided an overview of 17 cases of congenital hemangioma resulting in congestive heart failure. In all cases the lesions were larger than 7 cm in diameter and most complications (14/17) occurred postnatally. The majority of patients were treated by a combination of medical therapy (diuretics, digoxin, pressors and corticosteroids) and surgical embolization, ligation or resection. Three cases were diagnosed prenatally. One case presented with oligohydramnios at 40 weeks and postnatal transient thrombocytopenia, anemia and coagulopathy. After initial treatment with steroids, pressors and diuretics, the lesion was embolized followed by a good long-term outcome. Another case was complicated by high-output heart failure at 25 weeks’ GA. Maternal digoxin therapy resulted in improved fetal cardiac function. A cesarean section was performed at 38 weeks’ GA. Postnatal digoxin and corticosteroids were ineffective and the lesion was successfully resected after initial embolization. The third case comprised a giant congenital neck hemangioma of 14 cm at the time of cesarean section (34 weeks’ GA). The fetus showed the first signs of cardiac compromise at 20 weeks GA. Maternal digoxin was started at 30 weeks and 4 days’ GA and intramuscular (IM) dexamethasone sodium phosphate injected from 32 weeks and 3 days’ GA. Due to fetal hydrops, steroids were commenced at 33 weeks and cesarean section performed at 34 weeks’ GA. Unfortunately, the baby died within 12 h postnatally. These cases emphasize the importance of close prenatal monitoring in cases of congenital hemangiomata. If there is any sonographic evidence of fetal cardiac compromise, delivery in a center capable of treating the neonate, including potential embolization, or immediate postnatal transfer to such a center, is mandatory.

Despite not being specified, it is likely that these cases were all RICH lesions. As a consequence of the rapid proliferation of these fast-flow lesions in utero, trapped thrombocytes can result in thrombocytopenia, high-output cardiac failure, coagulopathy and anemia. Regular prenatal ultrasound assessment of the lesion (size, vascularity and calcification) as well as fetal welfare assessment including Doppler studies (umbilical artery pulsatility index and middle cerebral artery peak systolic velocity), assessment of the amniotic fluid, cardiac function and evidence of incipient fetal hydrops is recommended.

Furthermore, Weitz et al. [9] described an overall mortality rate of 30% as a result of congestive heart failure, with the majority of fatalities occurring in the first 21 days of life.

It is unclear whether the prenatal diagnosis of fetal distress could allow for prenatal treatment. Propranolol has been suggested as a potential therapy as it has proven to be successful in the setting of postnatal infantile hemangioma treatment. It causes vasoconstriction, inhibits proangiogenic signals and the induction of apoptosis of proliferating endothelial cells [10]. Dexamethasone sodium phosphate injections intramuscularly have been described to reduce the arteriovenous shunts in the hemangioma [11]. There is, however, no robust scientific evidence to support the antenatal use of propranolol or corticosteroids as the benefits are speculative, thus implementation in clinical practice is not currently recommended.

Maternal digoxin can be useful in case of fetal cardiac repercussions. Cordocentesis and fetal transfusion could be considered when fetal anemia becomes apparent. Further research on the efficacy and safety of the various prenatal treatment options is necessary [9].

Conclusion

We present on a case of a prenatally diagnosed rapidly involuting congenital haemangioma with an excellent long-term outcome. It is rare to diagnose these lesions prenatally, though literature provides evidence of the importance of prenatal diagnosis and monitoring. Given that these lesions can potentially lead to life-threatening congestive heart failure, with fetal demise previously reported, the emphasis should be on careful assessment of fetal welfare and surveillance for evidence of cardiac compromise or incipient hydrops. Prenatal diagnosis allows time for adequate counseling regarding the cause and natural history of the lesion and for decisions relating to mode, timing and place of delivery. In the absence of established delivery guidelines, each case should be individually assessed, keeping in mind that vaginal delivery can lead to birth trauma with significant and potentially life-threatening bleeding, particularly with large lesions. Whether prenatal treatment can be effective or should be implemented requires further research.