Management of Neonatal Hepatic Hemangiomas: A Single-Center Experience Focused on Challenging Cases

Abstract

Background: Management of hepatic hemangioma (HH) in infancy ranges from close monitoring to surgical resection. We analyzed the clinical characteristics and outcomes of HH according to its treatment options, with particular focus on challenging cases. Methods: Data of patients diagnosed with HHs in their first year of life and followed up for at least 1 year were retrospectively reviewed and divided into treatment and observation groups. Serial imaging results, serum alpha-fetoprotein (AFP) levels, medications, and clinical outcomes were compared. The detailed clinical progress in the treatment group was reviewed separately. Results: A total of 87 patients (75 in the observation group and 12 in the treatment group) were included. The median HH size at the initial diagnosis and the maximum size were significantly larger in the treatment group than the observation group (2.2 [0.5-10.3] cm vs. 1.0 [0.4-4.0] cm and 2.1 [0.7-13.2] vs. 1.1 [0.4-4.0], respectively; all p < 0.05]. The median initial and last serum AFP levels were significantly higher in the treatment group than in the observation group (76,818.7 vs. 627.2 and 98.4 vs. 8.7, respectively; all p < 0.05). Serum AFP levels in both groups rapidly declined during the first 3 months of life and were almost undetectable after 6 months. Among the challenging cases, a large (14 × 10 × 6.5 cm sized) focal HH was successfully treated using stepwise medical-to-surgical treatment. Conclusions: Patients with large HH and mild symptoms can be treated using stepwise pharmacotherapy. More aggressive surgical treatment of tumors unresponsive to initial pharmacotherapy may help shorten the treatment period and improve outcomes.

Keywords: alpha-fetoprotein; hepatic hemangioma; propranolol; sirolimus; treatment outcome.

Figure 1

Trends in HH size during the first 2 years of life. (A) Treatment group. (B) Observation group. Abbreviations: HH, hepatic hemangioma.

Figure 2

Serum AFP levels and half-life in the first 2 years of life. (A) Serum AFP levels in the treatment group. (B) Serum AFP levels in the observation group. (C) AFP half-life in the treatment group. (D) AFP half-life in the observation group. Abbreviations: AFP, alpha-fetoprotein.

Figure 3

The US and MRI images of Patient 7, who had a large HH that partially resolved after treatment using a single therapeutic agent. (A) US performed on the day of birth shows a 4.8 × 3.3 cm sized mass on the right liver. The patient had mild feeding difficulty. (B,C) MRI performed on the ninth day after birth shows a large congenital hemangioma in the right lobe of the liver (S8 and S5) with internal necrosis and hemorrhage. Oral propranolol was initiated. (D) US performed at the age of 6 months shows that the largest diameter of the lesion decreased to 3 cm after treatment using oral propranolol. Abbreviations: HH, hepatic hemangioma; AFP, alpha-fetoprotein; US, ultrasound; MRI, magnetic resonance imaging.

Figure 4

The US and MRI images of Patient 10, who had a large HH that partially resolved after step-by-step medical treatment. (A,B) MRI performed on the third day after birth shows an approximately 5.2 × 4.3 × 5.1 cm sized lobulated T2 hyperintense mass in the left lateral segment of the liver. The patient presented with feeding difficulty and abdominal distension. Oral propranolol was administered for 3 weeks from the 6th day of birth, and prednisolone was added at 1 month of age. (C) US performed at the age of 6 weeks revealed that the HH had increased in size up to 7.2 × 5.2 × 7.4 cm, with no improvement in symptoms. Oral sirolimus was initiated. (D) Follow-up US performed at 5 months of age shows that the tumor had decreased to 3.7 × 3.2 × 2.8 cm. Abbreviations: HH, hepatic hemangioma; US, ultrasound; MRI, magnetic resonance imaging.

Figure 5

The MRI scans of Patient 11, who underwent step-by-step medical treatment and surgical resection, which led to a complete resolution of the tumor. (A,B) Coronal and axial MRI performed on the fifth day of life shows a 14 × 10 × 6.5 cm sized, well-defined, and lobulated mass suggestive of HH. The patient presented with abdominal distension, vomiting, and respiratory difficulty. (C,D) Coronal and axial MRI performed at the age of 6 weeks shows a partial reduction in the mass without clinical improvement in symptoms, after hepatic artery embolization and the administration of oral propranolol, prednisolone, and sirolimus. Abbreviations: HH, hepatic hemangioma; MRI, magnetic resonance imaging.

Figure 6

Postoperative pathology results of Patient 11, who underwent stepwise medical treatment and surgical resection. (A) Gross appearance of excised large hemangioma. A multi-lobular yellowish mass (largest diameter, 11.2 cm) with irregular fibrosis and myxoid degeneration was observed. The mass was abutting Glisson’s capsule and 3 cm away from the hepatic parenchymal resection margin. (B) Hematoxylin and eosin stain, scan view. The mass showed widespread internal necrosis and multifocal dystrophic calcification, with only a focal viable tumor remaining. (C) Hematoxylin and eosin stain, 15× magnified view. A viable portion of the tumor showed variable-sized (capillary- to arteriole-sized) vascular lumens with internal erythrocytes, lined with bland-looking flat endothelial cells. (D) CD34 immunohistochemical staining, 15× magnified view. The tumor cells showed diffuse immunoreactivity to CD34, confirming the endothelial differentiation of the tumor.