Hepatic Angiosarcoma with eosinophilia: A Case Report and Literature Review

Introduction

Primary eosinophilia is relatively rare, whereas autoimmune, infectious, and inflammatory diseases, malignant tumors, and allergies can cause secondary eosinophilia. Treatment may be more effective for infectious diseases, inflammatory diseases, autoimmune diseases, and malignancies accompanied by eosinophilia.¹

Primary hepatic angiosarcoma (PHA) is a rare mesenchymal derived liver tumor, accounting for only 0.1% −2% of all primary liver malignancies.^2,3 Diagnosis of PHA is challenging due to its atypical symptoms and difficulties in distinguishing it from other malignancies through imaging. Surgical resection is the most effective treatment option, but most cases are already metastatic at diagnosis. Systemic or local chemotherapy can be used for palliative treatment. Anti-angiogenic therapy shows promise but lacks comparative efficacy data. In 1974, PHA was first reported by Block,⁴ since then, there have been relatively few data and reports on the diagnosis, treatment, and prognosis of this tumor owing to its rarity.⁵ This report is the first case of PHA with increased eosinophils, with missed surgical opportunity, unsuccessful targeted treatment, and fatal outcome, emphasizing the need for early detection and intervention in PHA cases.

Case Presentation

A 60-year-old female who had previously been in good health was admitted to our department on April 3, 2023, with the main complaint of loss of appetite for 3 months. One day prior, the patient visited a local hospital and underwent a full abdominal CT, which revealed a liver mass. Therefore, the patient was admitted to our hospital. The patient had no significant history of past illnesses. No notable personal or family medical history was reported. On admission, the physical examination was unremarkable, with a BMI of 23. Cardiac and pulmonary auscultation were normal, and there were no abnormalities detected in the liver, spleen, or subcostal regions upon palpation. No tenderness or pain was observed. Abnormal laboratory results, other liver function tests and tumor markers levels can be seen in Table 1. Further Improvement of Upper Abdominal MRI Enhancement revealed the following findings (Figure 1A and B): Diffuse multiple nodular and patchy abnormal enhancement lesions in the liver and spleen. The larger liver lesion measured approximately 2.2×2.1cm, while the larger spleen lesion measured about 6.5×5.5 cm. Considering the possibility of a parasitic infection, the patient exhibited an increase in eosinophils and multiple nodules in the liver and spleen. The patient denied any exposure to unclean drinking water or consumption of raw shrimp and crabs. To further investigate, a lung CT scan and an enhanced MRI of the head were performed (Figure 1C and D). No evident abnormalities were detected in the chest or intracranial region. However, multiple abnormal signal shadows with enhancement or metastatic tumors were observed in the skull. This raised questions about the presence of parasites or tumors in the brain and whether the changes in the liver, spleen, and skull could be attributed to the same underlying condition. The patient’s parasite antibody test came back negative (Table 1). As a result, we conducted multidisciplinary team (MDT) discussions on the matter. The patient underwent laparoscopic resection of the liver mass, and the subsequent postoperative pathology analysis (Figure 2A and B) confirmed the presence of hepatic angiosarcoma. Microscopic examination revealed the presence of spindle-shaped cells with frequent mitotic activity. Immunohistochemistry demonstrated positive expression of endothelial cell markers, including CD31, CD34, and CD99, as well as ERG. Additionally, the Ki-67 proliferative index was determined to be 50%. Ultimately, the diagnosis of hepatic angiosarcoma was definitively confirmed. Chemotherapy is recommended, but the patient refused. The latest report shows⁶ that patients have achieved effective treatment through TACE (Transcatheter arterial chemoembolization) and treatment with Anlotinib plus Camrelizumab. So targeted treatment with anlotinib was given, but after 2 months, the patient died of splenic rupture and bleeding. The patient’s clinical course timeline is shown in Figure 3.

Table 1 Laboratory Results

Figure 1 (A and B) Upper abdominal MRI enhancement: April 3, 2023: Diffuse multiple nodular and patchy T1WI low signal and T2WI mixed high signal shadows can be seen in the liver and spleen parenchyma, with unclear boundaries. The enhanced scan shows centripetal filling enhancement, some show mild enhancement, and some do not. (C and D) Enhanced cranial magnetic resonance imaging, April 7, 2023. Multiple strip shaped abnormal signal shadows in the skull are seen, showing low signal on T1WI, high signal on T2WI and FLAIR, high signal on DWI, equal or low signal on ADC, and boundary Insufficient clarity, significantly enhanced after enhancement.

Figure 2 (A and B) Liver pathology, April 24, 2023: Spindle cell tumor (liver mass), with frequent mitosis and tendency towards malignancy.

Figure 3 Timeline of patient’s clinical course.

Discussion

Hemangiosarcoma belongs to a group of adult soft-tissue sarcomas, and among them primary hepatic angiosarcoma (PHA) is a rare mesenchymal tumor with a worse prognosis compared to other angiosarcomas. Although exposure to vinyl chloride, has been associated with PHA in some cases, the exact causes are still unclear for most patients. However, there is no evidence that these factors were involved in this patient.

PHA lacks specific symptoms, but presents with non-specific complaints such as stomach discomfort, fatigue, poor appetite, weakness, and a feeling of heaviness.⁷ The most common fatal and poorest prognosis are splenic rupture⁸ and bleeding, as in our case the patient died of spontaneous splenic rupture and ultimately hemorrhagic shock.

Diagnosis mainly relies on pathological examination since distinguishing PHA from other malignant tumors using ultrasound, CT, or MRI is challenging. Early detection is crucial as PHA can be misdiagnosed as a hemangioma in the early stages, and surgical resection is necessary to prevent malignant progression.⁶ Only a small percentage of patients eligible for surgical resection, which has shown effectiveness and long-term survival in some cases. However, most cases of liver angiosarcoma are already metastatic at the time of diagnosis and cannot be treated surgically.⁹ Tumors smaller than 10 cm are the only favorable factor for partial hepatectomy.¹⁰ For patients who are not candidates for surgery, systemic or local chemotherapy can be used as palliative treatment. Anti- angiogenic therapy shows promise but comparing the efficacy of different treatment strategies is challenging due to the limited number of patients and the use of diverse drugs. Neeraj¹¹ reviewed 23 patients with hepatic vascular sarcoma revealed a median overall survival (OS) was 6 months, with 71% of patients receiving systemic chemotherapy and 29% receiving immunotherapy. 14% of patients underwent surgery or local treatment with radiation embolization. Wilson¹² retrospective showed Forty-four patients with hepatic angiosarcoma, only 10 patients underwent surgical resection. Median overall survival was 5.8 months and 1-, 3-, and 5-year actual survival was 30.0%, 8.1%, and 5.6%, respectively. A prospective study conducted by Tripke et al¹³ reported Nine patients who underwent surgical resection with median follow-up was 15.5 months. Mangla¹⁴ analyzed 346 patients with PHA, with one- third (35.7%) received chemotherapy, and 14.6% underwent a surgical resection. The median survival was 1.9 months, with a higher median survival rate of 7.7 months for surgical resection. The median survival rate for patients receiving chemotherapy is higher than that for those not receiving chemotherapy. An overall summary of cases and characteristics of primary hepatic angiosarcoma from previous retrospective and prospective studies is presented in Table 2.

Table 2 An Overall Summary of Cases and Characteristics of Primary Hepatic Angiosarcoma

The case presented involves a patient who sought medical attention due to decreased appetite and was found to have an elevated eosinophils count. Abdominal CT revealed multiple liver nodules, and surprisingly, high-density metastatic lesions were also found in the skull. Tumor markers only show CA125 Slight elevation. A laparoscopic biopsy confirmed the diagnosis of hepatic angiosarcoma, but the opportunity for surgical intervention had been missed. Although less invasive biopsies or even cytological examination have a good diagnostic yield in the diagnosis of sarcoma,¹⁷ especially in patients not eligible for excisional surgical therapy. Koyama et al¹⁸ reported a 78% success rate for biopsy, to ensure a positive detection, the MDT recommended laparoscopic extraction of the liver nodules for further examination instead of ultrasound-guided liver puncture biopsy. Consequently, the patient underwent laparoscopic resection of the liver mass. The present study showed that PHA expresses at least one among CD31, CD34, and that the Ki-67 increase, which is a common diagnostic feature of angiosarcoma.¹⁹ In this study, CD34 (+), CD31 (+), and Ki67 (about 50%) expression was consistent with that reported in the literature.¹⁵ we find CD99+, as it was reported to have an adverse prognostic role and to correlate with the development of distant metastases in angiosarcomas in other settings.²⁰ Targeted treatment with Anlotinib was administered for two months, but the patient’s condition did not significantly improve. Eventually, the tumor ruptured, leading to bleeding and the patient’s death.

Conclusion

In clinical practice, PHA awareness should be raised, and early biopsy of lesions should be performed based on symptoms. The provides a pathological basis for subsequent treatment selection and further assist in clinical diagnosis and treatment.