Spontaneous intracapsular hemorrhage of a giant hepatic cavernous hemangioma: a rare case report and literature review

Background Hepatic cavernous hemangioma is the most common type of benign liver tumor. Although ruptures and hemorrhages of hepatic hemangioma are rare complications, they are associated with high mortality. Most practitioners only pay more attention to abdominal hemorrhages caused by the rupture of hepatic hemangiomas. However, spontaneous intracapsular hemorrhages can often be neglected and poorly understood. Case presentation A 65-year-old man was referred to our institution with right upper quadrant pain, which had occurred suddenly and without a history of recent trauma. The blood test results were normal. Magnetic resonance imaging (MRI) of the abdomen showed a cystic mass in the right liver lobe. Considering the possibility of hepatic cystadenoma with hemorrhage, the patient underwent a right hepatic lobectomy. The pathological findings unexpectedly revealed intratumoral hemorrhage of hepatic hemangioma. The patient recovered well and was discharged eight days after surgery. Conclusions Intracapsular hemorrhage of hepatic cavernous hemangioma is challenging to diagnose and has a high potential risk of rupture. MRI is beneficial for diagnosing subacute internal hemorrhage cases, and it is recommended to undergo surgery for patients with a definitive diagnosis.


Background
The cavernous liver hemangioma is the most common benign tumor of the liver, and its pathogenesis is still unclear. It is common in middle-aged women [1]. Most of the patients with hepatic hemangioma have no clinical symptoms and are only followed up. Treatment is necessary when the tumor size increases to the point of causing symptoms such as abdominal discomfort, vomiting, poor appetite, even serious complications such as tumor rupture or bleeding [2][3][4]. Although hepatic hemangioma rupture and hemorrhage are uncommon complications, they can be lethal [5,6]. Spontaneous intracapsular hemorrhage of cavernous hepatic hemangioma is rare. There are only eight Chinese or English reports in the past 26 years [7][8][9][10][11][12][13][14], which causes a lack of in-depth understanding. The author reports a patient diagnosed pathologically with intracapsular hemorrhage of hepatic hemangioma and reviews the relevant literature at home and abroad, which could help us better understand it.

Case presentation
A 65-year-old man was referred to our hospital experiencing a persistent dull pain in the upper right abdomen lasting 5 days. Initially, he visited a local hospital, where Open Access *Correspondence: 64740052@qq.com 3 Department of Ultrasound Diagnostics, Guangdong Province, The Affiliated Hospital of Guangdong Medical University, 57th, Renmin South Road, Xia shan District, Zhanjiang 524001, People's Republic of China Full list of author information is available at the end of the article a Color Doppler ultrasound revealed a giant cystic mass, which was more likely to undergo intracapsular hemorrhaging. It had occurred suddenly without a history of recent trauma. He had no history of viral hepatitis or a family history of cancer and recently lost weight. On physical examination, his conjunctiva was not pale, and jaundice was not observed in his sclera. His liver was not palpable below the costal margin. There was tenderness in the right liver area, a negative Murphy's sign. Laboratory examinations showed a white blood cell count of 6.04 × 10 9 /L (normal range: 4-10 × 10 9 /L), a red blood cell count of 3.75 × Tests revealed that HBsAg was negative, anti-HBs Ab was positive, and anti-HCV Ab was negative. Concentrations of all tumor markers were also determined and showed an alpha-fetoprotein (AFP) level of 1.65 ng/ mL (normal range: 0-9 ng/mL), a carbohydrate antigen 19-9 (CA 19-9) level of 5.59 U/mL (normal range: 0-27 U/mL), and a carcinoembryonic antigen (CEA) level of 0.28 ng/mL (normal range: 0-5 ng/mL). Abdominal MRI revealed an 11.3 cm × 8.2 cm × 9.9 cm cystic mass in the right lobe of the liver, with multiple-room and an uneven signal (Fig. 1 arrow). The lesion showed isointense or hyperintense signals on T1-weighted images and on T2-weighted images ( Fig. 1A-B arrows). After the contrast material agent's infusion, an unenhanced lesion was found in the cyst ( Fig. 1 C-E). The preoperative diagnosis was hepatic cystic adenoma hemorrhage or hepatic cyst hemorrhage. There was no effusion in the abdominal cavity during the operation, no obvious cirrhosis, and a giant cystic mass was located in the liver's right lobe. The cystic mass's maximum diameter was about 12 cm, intact, and no bleeding was detected. The capsule of the mass was close to the bifurcation of the right portal vein. The patient underwent a right hepatic lobectomy. We observed that the resected specimen was multipleroom and found necrotic materials and hemorrhagic components (Fig. 2). The operation was successful, and the patient was administered anti-inflammation, liver protection, and pain relief. Microscopically, the tumor was composed of dilated blood vessels that were lined with flat endothelial cells, a localized hemorrhage, and cystic changes (Fig. 3a). Immunohistochemistry staining showed that endothelial cells were CD31, CD34, and D-240 positive (Fig. 3b-d). The patient recovered well and was discharged 8 days after the surgery. One month after surgery, MRI scans revealed remnant liver volume increased significantly and showed no encapsulated peritoneal effusions (Fig. 1f ).
Similar articles were obtained using the keywords "hepatic hemangioma, internal hemorrhage" through searching "PubMed, National Library of Medicine, Web of Science, VIP database, China National Knowledge Infrastructure (CNKI), and Wan fang database for articles from January 1995 to January 2021. We retrieved only 8 cases reported in Chinese or English. Patient data, including author, gender, age, preoperative diagnosis, and treatment procedures, were extracted. We summarized the relevant findings in Table 1. There were seven females and one male, aged from 29 to 70 years, with a mean age of (49.3 ± 13.7) years. Lesions were located in the right lobe (n = 2), the left lobe (n = 4), left and right lobes (n = 1), and the caudate lobe (n = 1). The tumor sizes ranged from 4 cm to the whole hepatic lobe.
All patients had no history of trauma. The methods of diagnostic Imaging included Computed Tomography (CT), MRI, or Ultrasound. The six patients underwent surgery directly; one patient first underwent a transcatheter arterial embolization (TAE), then agreed to liver resection, while one selected TAE due to pregnancy. All

Discussion and conclusions
Cavernous hemangioma is most common in the liver. The cause of the disease is not clear; it is believed that it may be related to abnormal vasculogenesis and angiogenesis [15]. Hepatic hemangiomas grow slowly, and the course of the disease lasts for several years. There are no clinical symptoms when the tumor is small. As the tumor size increases, it causes abdominal discomfort or pain, vomiting, fever, and belching [16]. Besides Kasabach-Merritt syndrome, most doctors often focus on abdominal hemorrhages caused by the rupture of hepatic hemangiomas. However, reports on hepatic hemangioma with internal hemorrhage are rare, causing a lack of further understanding and ignoring its serious harmfulness.
Patients with hepatic hemangioma have different clinical symptoms, and abdominal pain is the most common symptom. The majority of patients only have upper abdominal pain; however, typical hepatic hemangioma rupture symptoms include sudden, severe abdominal pain, massive abdominal bleeding or hemorrhagic shock, etc. Fever, however, is a very rare symptom. In the mentioned cases, three patients had fever symptoms, one of which was first diagnosed as a liver abscess [12], but the response to anti-inflammatory drugs was inadequate.
After an ultrasound-guided liver biopsy, the tissue samples showed blood clots, showing intratumoral bleeding. Another patient diagnosed with intracapsular hemorrhage of hepatic hemangioma had fever and cough symptoms, and the anti-inflammatory effect was poor. The relevant examination excluded other infection causes, then the fever symptoms disappeared after hepatectomy. As for large hemangiomas, especially with a diameter > 10 cm, we theorize the fever's cause was necrotic changes within the hemangioma.
With the improvement of health conditions and people's health awareness, more and more patients with hemangioma of the liver have been found. Hemangioma is diagnosed with various imaging techniques such as ultrasound, CT, MRI, angiography, positron emission tomography (PET), which provide a diagnostic accuracy of > 90% [17]. MRI is more specific than CT in diagnosing subacute intratumoral hemorrhage, which shows high intensity on T1-and T2-weighted images [18]. However, it is sometimes difficult for patients without a medical history of liver hemangioma to distinguish from an intracapsular hemorrhage of hepatobiliary cystadenoma, hepatic cysts, or even liver cancer. Among the eight literatures reviewed in this paper, only 2 cases were confirmed as intratumoral hemorrhage before the operation.
Hepatic hemangiomas grow slowly, and the course of the disease lasts for several years. There are no clinical symptoms when the tumor is small. When the diameter is > 4 cm, which is categorized as a "giant hemangioma" that causes abdominal discomfort or pain as the tumor size increases [19]. The incidence of abdominal bleeding caused by ruptured hepatic hemangioma is relatively low (1-4%) [20], and the mortality is quite high (36-39%) [21]. Therefore, for patients with clinical symptoms, intense surgery demands and high-risk complications should be actively treated. The treatment methods for hepatic hemangiomas include surgical resection, TAE, liver transplantation, microwave coagulation, radiofrequency therapy, and radiological therapy [22][23][24]. Recently, there have been reports of drugs for hepatic hemangiomas [25]. We report a patient admitted to the hospital for right upper quadrant pain. Considering the possibility of hemorrhage in the hepatic cystadenoma, We evaluate the patient's operative tolerance and the remaining liver volume. The patient underwent right hepatic lobectomy and cholecystectomy. Intracapsular hemorrhage of hepatic cavernous hemangiomas is very rare, which is difficult for us to distinguish from hepatic cyst masses with an intratumoral hemorrhage or even malignant liver tumors. Due to the high mortality of tumor rupture, appropriate treatments are recommended as soon as possible after diagnosis.