1 Introduction

Congenital hepatic hemangiomas (CHHs) are uncommon benign vascular tumors that proliferate in utero and are fully grown by birth [1]. On the basis of the different clinical regression cycles, CHHs are currently categorized into three types: rapidly involuting congenital hemangioma (RICH), noninvoluting congenital hemangioma (NICH), and partially involuting congenital hemangioma (PICH). RICH completely regresses within 12–18 months, NICH grows in proportion to body growth, and PICH initially shows regression similar to RICH but stops growing later [2-4].

At present, the prenatal diagnosis of CHH mainly depends on an imaging examination. According to the clinical treatment guidelines [3], fetal CHH can be diagnosed by the clinical outcome and imaging methods and generally does not require a pathological examination. To better understand the natural history of CHHs, the “Guidance Document for Hepatic Hemangioma (Infantile and Congenital) Evaluation and Monitoring” recommends continued monitoring of a CHH for at least 1 year [3].

In addition, although benign by pathology, CHHs have variable presentations ranging from asymptomatic to life-threatening complications in utero [5]. These complications include high-output cardiac failure with and without hydrops, abdominal compartment syndrome, hemolytic anemia, severe thrombocytopenia with disseminated intravascular coagulopathy (Kasabach–Merritt sequence), and hepatic dysfunction [6-8]. Therefore, a prenatal diagnosis, postnatal follow-up, and prompt detection of complications are essential for identifying and treating CHHs. To date, there have only been a few case studies that evaluated prenatal and postnatal imaging (ultrasound and magnetic resonance imaging [MRI]) features of CHH. To the best of our knowledge, no studies have examined the differences between imaging features and morphological characteristics of different-sized CHHs or performed a long-term follow-up.

Therefore, this study aimed to analyze the prenatal ultrasound and MRI findings of CHHs, to examine the imaging characteristics of CHHs of different sizes, to describe the natural history of CHHs, and to report the clinical outcomes of these patients. Our findings will provide a basis for the clinical diagnosis and evaluation of the prognosis of CHHs.

2 Materials and Methods

In this observational, retrospective study, all ultrasound and magnetic resonance images of fetuses diagnosed with CHH from 1 January 2016 to 1 December 2023 were reviewed. The diagnosis of CHH was made according to the International Society for the Study of Vascular Anomalies classification system, using multimode diagnostic methods combined with clinical manifestations, imaging features, and/or histopathological confirmation [2].

Using the maximum diameter of the lesion, we divided the patients into two groups (diameter < 4 cm group and diameter ≥ 4 cm group). The inclusion criteria included a liver mass diagnosed as CHH by a combination of prenatal ultrasonography and MRI and confirmed by postnatal MRI examinations, serial ultrasound examinations, or pathology results. Cases of CHH without follow-up results, those with termination of the pregnancy, or those proven to be hepatoblastoma were excluded. In fetuses who met the inclusion criteria, pregnancy and delivery outcomes were retrieved and reviewed. In live-born infants, neonatal evaluations with clinical confirmation of CHH were reviewed. In asymptomatic cases, serial images were observed to monitor the regression. This study adhered to the principles of the Declaration of Helsinki and was approved by the Ethics Committee of Shandong Provincial Hospital Affiliated to Shandong First Medical University (No. 2019-001). Informed consent was obtained from the parents/guardians of all patients.

3 Results

3.2 Imaging Features

All 36 cases of CHHs were focal, including 22 cases in the right lobe and 14 cases in the left lobe. The boundary of 34 (94.4%) tumors was clear, and 2 (5.6%) tumors with an unclear boundary were located in the diameter > 4 cm group. In two-dimensional ultrasound images, 75% of the CHH tumors showed mixed echoes, and internal tubular anechoic structures of varying thickness were visible. However, mixed echoes were significantly more common in the diameter ≥ 4 cm group than in the diameter < 4 cm group (p = 0.026). In addition, two fetuses showed abnormal enlargement of the cardiothoracic ratio, and both were in the ≥ 4-cm-diameter group. In color Doppler flow images, 94.4% of the tumors had an abundant blood supply, and the blood supply of the hepatic portal vein was visible. In addition, 95% of the tumors were surrounded by circular or semicircular blood flow signals.

CHH was hyperintense on half-Fourier acquisition single-shot turbo spin-echo and fast imaging with steady-state precession images and relatively hypointense compared with the normal liver parenchyma on T1WI. However, the findings widely varied. In the < 4-cm-diameter group, CHH appeared more homogeneous, and CHHs in the ≥ 4-cm-diameter group had a more complex and heterogeneous appearance, such as necrosis (p = 0.023) and dilated intrahepatic vessels (p = 0.030), than those in the < 4-cm-diameter group (Figure 1). Thin distal abdominal aortas (18.8%) were also observed in large CHH cases. After birth, an early phase enhancement pattern was typically peripheral with a nodular distribution of contrast enhancement, and the delayed phase showed a centripetal fill-in pattern. The details of prenatal imaging features of the CHHs are summarized in Table 2.

TABLE 2. 36 cases of congenital hepatic hemangioma prenatal imaging characteristics.

Imaging features	Total (n = 36)	CHH (0–4 cm) (n = 20)	CHH (> 4 cm) (n = 16)	p
Sex				0.999
Male	17 (47.2)	9 (45.0)	8 (50.0)
Female	19 (52.8)	11 (55.0)	8 (50.0)
Location				0.515
Right lobe	22 (61.1)	11 (55.0)	11 (68.8)
Left lobe	14 (38.9)	9 (45.0)	5 (31.2)
Boundary				0.190
Clear	34 (94.4)	20 (100.0)	14 (87.5)
Unclear	2 (5.6)	0 (0.0)	2 (12.5)
Echogenicity				0.026
Homogeneity	9 (25.0)	8 (40.0)	1 (6.2)
Heterogeneous	27 (75.0)	12 (60.0)	15 (93.8)
Rich internal blood supply	34 (94.4)	18 (90.0)	16 (100.0)	0.492
Marginal blood flow	31 (86.1)	16 (80.0)	15 (93.8)	0.355
Cardiothoracic ratio				0.190
Abnormal	34 (94.4)	20 (100.0)	14 (87.5)
Normal	2 (5.6)	0 (0.0)	2 (12.5)
Intralesional hemorrhage	7 (19.4)	2 (10.0)	5 (31.2)	0.204
Necrosis	14 (38.9)	4 (20.0)	10 (62.5)	0.016
Shunting	2 (5.6)	0 (0.0)	2 (12.5)	0.190
Dilated intrahepatic vessels	7 (19.4)	1 (5.0)	6 (37.5)	0.030
Thin distal abdominal aorta	3 (8.3)	0 (0.0)	3 (18.8)	0.103

• Note: The bold values indicate that the difference is statistically significant (p < 0.05). Data are presented as n (%).

3.3 Growth Patterns/Natural History of CHHs

Infants who were not treated after birth were followed up regularly and consecutively. The changes in volume of the tumor at each follow-up in each child were also recorded (Figure 2a). A total of 18 (54.5%) cases were classified as RICH (Figure 3), 9 (27.3%) as PICH, and 2 (6.1%) as NICH. Additionally, a new type of CHH was identified in which four (12.1%) cases continued to proliferate after birth and spontaneously subsided in subsequent months (Figure 4). A nonparametric test showed that the average volume of CHHs decreased with an increase in age (Figure 2b). The volume of CHHs did not show significant age-related changes before 6 months of age. However, a significant decrease in CHH volume occurred after 9 months of life compared with that at birth (p = 0.001).

4 Discussion

This study showed that the imaging features of CHHs were diverse. Smaller CHHs were usually homogeneous, whereas larger CHHs tended to be more commonly heterogeneous because of hemorrhage and necrosis. CHH had a natural regression process, and the tumor was significantly regressed after 9 months. We also identified a new type of CHH with postnatal proliferation followed by spontaneous regression. The patients with CHH showed a good prognosis if the lesion did not cause complications at birth, but some complications of CHHs can be fatal. These findings are important because they contribute to clinical outcome predictions for patients with CHHs. There is a lack of large-scale data on the natural history of CHHs. Therefore, this study provides useful data on the interpretation and understanding of the evolution of CHHs.

In our study, most CHHs were detected during the third trimester, and the initial diagnosis was typically established at a mean gestational period of 34 weeks. The time frame for detection spanned from the 25th to the 39th weeks of pregnancy. These findings are consistent with previous case series studies [8, 11]. In this study, all 33 cases of CHHs of fetuses were single lesions, and 61.1% of the tumors were located in the right hepatic lobe. These findings are consistent with a report by Isaacs [12].

Our study also showed that the imaging features of CHH were significantly associated with the size of the lesion. These findings are consistent with a previous study, which showed that smaller hemangiomas were homogeneous, whereas larger hemangiomas included calcifications, cystic spaces, hemorrhages, necrosis, and fibrosis [3]. Severe complications are more likely to occur in CHHs with a tumor diameter ≥ 4 cm than in those with a tumor diameter < 4 cm. Therefore, in the clinical setting, more attention should be paid to large CHHs and timely treatment if complications occur.

The growth patterns of CHHs in our study were different from those in previous studies [13]. In our study, 93.9% of cases were completely or partially resolved, and 6.1% of cases were NICH. However, four cases showed a proliferative trend during the first 6 months of life followed by spontaneous regression in the following months. In previous studies, this pattern was thought to be characteristic of infantile hemangioma. This pattern is different from the definition of CHH, which states that CHHs proliferate in utero and are fully formed at birth. Our study findings complement the current knowledge that CHHs can also show a tendency of initial proliferation followed by spontaneous regression over several months. Nevertheless, we found that the fastest decline in CHH volume occurred 9 months after birth. This finding could help clinical outcome predictions for patients with CHHs.

Regarding long-term clinical outcomes, all cases in our study were asymptomatic, except for one case with a large CHH with a volume of 376.38 cm³. The patient did not survive because of severe complications from congestive heart failure at birth. This finding indicates that a large CHH can be an adverse prognostic factor [14].

This study has some limitations. First, the results might have been affected by the relatively small sample size. Therefore, we will continue to collect further relevant data from new eligible participants to increase the sample size and power of this study. However, because of the rarity of CHHs in fetuses, this study is the largest case–control study on the subject to date. Second, histological or genetic markers were not identified to differentiate between RICH and NICH in our study. Future studies should include more follow-up data to investigate the underlying mechanisms of CHH, examine histological and genetic findings, and determine differences between different types of CHHs.

5 Conclusions

We report the prenatal ultrasound and MRI features of CHHs and found differences in acoustic shadows with different diameters. The trend of tumor regression was examined, and a new type of CHH was identified. The combination of MRI and ultrasound can improve the diagnostic level of CHH, which is beneficial for the reasonable management of pregnancy and the prediction of clinical outcomes of patients with CHHs.

Author Contributions

Luyao Yang: data curation (lead), investigation (lead), validation (lead), visualization (lead), writing – original draft (lead). Jianbo Teng: conceptualization (equal), methodology (equal), supervision (equal), writing – review and editing (equal). Xinhong Wei: conceptualization (lead), methodology (lead), project administration (lead), resources (lead), supervision (lead), writing – review and editing (lead).

Ethics Statement

This study adhered to the principles of the Declaration of Helsinki and was approved by the Ethics Committee of Shandong Provincial Hospital Affiliated to Shandong First Medical University (No. 2019-001).

Consent

Informed consent was obtained from the parents/guardians of all patients.

Conflicts of Interest

The authors declare no conflicts of interest.