Microwave ablation and transcatheter arterial chemoembolization for hepatic epithelioid hemangioendothelioma two case reports with literature review

Abstract

Background

Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular sarcoma in which surgical resection or liver transplantation is often not feasible due to multifocal or unresectable disease. Although various non-surgical treatments, including chemotherapy, targeted therapy and immunotherapy have been employed, their effectiveness remains inconsistent. Consequently, there is limited data on durable, minimally invasive treatment strategies. This report presents the long-term outcomes of two distinct, minimally invasive treatment strategies, staged microwave ablation (MWA) alone and transcatheter arterial chemoembolization (TACE) followed by MWA, highlighting their potential for durable disease control.

Case description

We describe two patients with pathologically confirmed, unresectable HEHE who achieved sustained complete response (CR). Case 1 was a 47-year-old woman with multifocal HEHE that progressed despite prior systemic therapy. She underwent staged MWA and maintained CR for 40 months according to mRECIST criteria. Case 2 was a 53-year-old man with multiple large, confluent hepatic lesions (largest diameter 6.9 cm) treated with combined TACE and MWA, achieving CR maintained for 84 months, with substantial tumor regression and no recurrence.

Conclusions

In two patients with unresectable HEHE, staged MWA alone or TACE followed by MWA was associated with durable radiologic complete responses. These observations warrant validation in larger multicenter cohorts with standardized response and safety reporting.

Introduction

This manuscript is written following the CARE checklist.

Background

Hepatic epithelioid hemangioendothelioma (HEHE) is a rare sarcoma of vascular origin, arising from vascular endothelial cells [1, 2]. Surgical resection and liver transplantation are primary therapies for HEHE. For patients ineligible for surgery or transplantation, no standardized treatment strategy has been established. Systemic therapies, including chemotherapy, antiangiogenic agents, and targeted therapy, have demonstrated variable and often limited efficacy [3]. Locoregional treatments such as TACE, radiofrequency ablation, and MWA have been reported as alternative options, primarily in small case series and isolated reports [1, 4].

Rationale and knowledge gap

Given the limited effectiveness of these therapies, there is a growing need to explore interventional treatments that may offer improved disease control in patients with unresectable or multifocal HEHE. While microwave ablation (MWA) and transcatheter arterial chemoembolization (TACE) have been used in other liver tumors, their roles in HEHE remain underreported and poorly studied clinically.

Objective

This study presents two cases of multifocal HEHE treated with MWA alone and MWA combined with TACE, respectively. We also review the relevant literature to evaluate the potential role and therapeutic value of interventional approaches in the management of HEHE.

Case presentation

All patient data have been de-identified, and written informed consent was obtained from both individuals. Peri-procedural and follow-up complications were extracted from the medical records and graded according to the Society of Interventional Radiology (SIR) classification system [5].

Case 1

A 47-year-old woman with no significant past medical history was incidentally found to have hepatic lesions during a routine ultrasound on April 20, 2021. Abdominal magnetic resonance imaging (MRI) revealed multiple ovoid intrahepatic lesions. The largest measured approximately 4.5 × 2.9 cm and showed partial confluence. On T1-weighted imaging, the lesions were hypointense with a markedly hypointense core, while T2-weighted imaging showed hyperintense lesions with central hyperintensity (Fig. 1A). In the portal venous phase, contrast-enhanced images demonstrated lesions with peripheral and central hypoenhancement, separated by an intermediate enhancing band (Fig. 1B). Laboratory tests, including tumor markers, were within normal limits.

Fig. 1.

Case 1, a 47-year-old female treated with staged MWA. A, B: Pre-treatment contrast-enhanced MRI reveals multiple lesions in the right hepatic lobe, located in segments V and VI. On T2-weighted imaging, the lesions display a targetoid appearance with a center that is hyperintense relative to the periphery. In the portal venous phase, the lesions are hypointense at the core and periphery, with an interspersed high-signal enhancing band centrally. C, D: The first MWA session involved a dual-probe ablation of the confluent lesion in segment V (4.9 cm × 3.0 cm), followed by ablation of the lesion in segment VI (2.1 cm × 1.8 cm). E: Immediate post-procedural contrast-enhanced CT shows expected post-ablation changes. F, G: Pre-procedural imaging before the second ablation session demonstrates multiple lesions in segment VIII of the right hepatic lobe, with respective diameters of 4.5 cm × 3.0 cm, 3.1 cm × 1.4 cm, and 3.0 cm × 1.8 cm. H: The second ablation procedure targeting the multiple lesions in the right lobe. I, J: A 40-month follow-up contrast-enhanced MRI demonstrates stable post-ablation changes. The lesions exhibit cystic signal changes on T2-weighted images with no definitive enhancement post-contrast, consistent with a complete response

A liver biopsy performed at an outside institution confirmed the diagnosis of hepatic epithelioid hemangioendothelioma (HEHE), with a Ki-67 proliferation index of 2%. The patient was initially managed with systemic therapy, starting with oral lenvatinib (8 mg once daily), which was later switched to anlotinib (12 mg once daily). However, follow-up imaging at three months revealed slight progression of the largest lesion, which had increased to 4.9 cm in diameter. Therefore, the patient was referred to our interventional radiology department.

Given her ineligibility for surgical resection and disease progression despite targeted therapy, staged MWA was initiated as a locoregional strategy, supported by prior reports in HEHE. On August 26, 2021, the patient underwent her first session of percutaneous, CT-guided MWA (Siemens SOMATOM go.Now, 16-slice) under general anesthesia. Two 18-gauge microwave probes (ECO-100A1; Nanjing Ecotron, China) were used to ablate two lesions measuring 4.9 × 3.0 cm and 2.1 × 1.8 cm, respectively. The procedure involved six ablation sites at 50 W for a total of 30 min (Fig. 1C–E). Post-procedure, the patient experienced mild anemia and lumbar discomfort, both managed conservatively (SIR minor complication). A second MWA session was performed on October 28, 2021, using two probes and six ablation sites at 40–50 W for 30 min (Fig. 1H). The patient recovered without complications. Serial surveillance contrast-enhanced MRI over 40 months showed only post-ablation changes, with no residual or recurrent disease (Fig. 1I, J).

Case 2

A 53-year-old male with a history of chronic hepatitis B infection was found to have multiple low-density hepatic lesions during a routine health screening on September 6, 2017. A subsequent positron emission tomography–computed tomography (PET-CT) scan at an outside institution confirmed multiple low-attenuation lesions in the right posterior hepatic lobe, showing increased fluorodeoxyglucose (FDG) uptake consistent with malignancy. The liver biopsy indicated ballooning degeneration and steatosis of hepatocytes, with minimal lymphocytic infiltration in the portal tracts. In fibrotic regions, tumor cells were arranged in cords and strands, exhibiting mild nuclear atypia and intracytoplasmic vacuoles. Immunohistochemistry was negative for hepatocyte paraffin 1 (Hep Par 1) and alpha-fetoprotein (AFP), but positive for CD34, CD31, and vimentin. The pathological findings confirmed a diagnosis of HEHE.

On November 27, 2017, the patient received TACE combined with MWA. Because the largest lesion (6.9 × 3.2 cm) was adjacent to the diaphragm, we performed TACE first to reduce tumor perfusion and procedural risk, followed by MWA for local tumor control. During the TACE procedure, the angiography of the phrenic and aberrant right hepatic arteries showed an abnormal tumor blush, and the feeding arteries were super selectively catheterized. An emulsion was prepared by mixing oxaliplatin (20 mg) with iodized oil (10 mL). A total of 3.5 mL of the emulsion was slowly injected into the arteries, followed by 100–300 μm bland microspheres (Fig. 2E–H). Immediately after TACE, MWA was performed under general anesthesia using two probes. Ablation was performed at six sites within the right hepatic lobe at 40–50 W for a total of 28 min (Fig. 2I, J).

Fig. 2.

Case 2, a 53-year-old male treated with TACE combined with MWA. A, B Pre-treatment MRI shows a lesion in segment VIII of the right hepatic lobe that is heterogeneously hyperintense on T2-weighted imaging, measuring 3.3 cm × 3.1 cm and exhibiting a “targetoid” appearance. C, D: Multiple, plaque-like abnormal signals are visible in the right hepatic lobe. The largest lesion measures approximately 6.9 cm × 3.2 cm and is partially confluent with adjacent smaller lesions. E-H: Intra-procedural angiography during TACE reveals abnormal tumor staining supplied by the phrenic and aberrant right hepatic arteries. These feeding arteries were superselectively catheterized and embolized. I, J: A dual-probe MWA was performed to ablate the multiple lesions in the right lobe. K, L: An 84-month follow-up contrast-enhanced MRI shows a significant reduction in lesion size, indicating successful coagulative necrosis

The remaining lesions were subsequently treated over three additional MWA sessions, as detailed in Table 1. Serial surveillance MRI over 84 months demonstrated marked lesion regression and durable CR (Fig. 2K, L).

Table 1.

Tumor Information and Treatment Outcomes

Patient number	Case 1	Case 2
Age(years)/Sex	47/Female	53/Male
Number of Tumors	5	5
Tumor Diameter (cm)a	3.0 (2.1–4.9)	2.9 (2.3–6.9)
Number of Procedures	2	5
Treatment Modality	MWA	TACE + MWA
Follow-up Duration (months)	40	84
mRECIST	CR	CR

^aTumor diameter presented as median (range)

CR: complete response

Discussion

HEHE is a rare vascular sarcoma of low-grade malignancy, with an annual incidence of less than one case per million. The disease has a higher incidence in females than in males [1, 2, 6]. Clinically, HEHE typically presents with multifocal liver lesions with an indolent growth pattern. Despite its indolent progression, HEHE has metastatic potential, with the lungs and bone being the most common sites of distant spread [1]. The clinical presentation of HEHE is highly variable; while some patients present with constitutional symptoms such as abdominal pain, a palpable mass, weight loss, fatigue, or anemia, a significant portion—including those in this report—may be entirely asymptomatic at diagnosis [1, 6, 7]. The histopathological hallmark of HEHE is the infiltrative growth of epithelioid endothelial cells accompanied by a fibrous or myxohyaline stroma, often forming irregular vascular channels. Immunohistochemical analysis is critical for diagnosis, characteristically demonstrating positive staining for vascular markers such as CD31, CD34, and vimentin, while hepatocellular markers like HepPar-1 and AFP are typically negative [6, 8]. Currently, there are no specific laboratory tests for HEHE. Complete blood counts and coagulation profiles are typically unaffected, and serum tumor markers are within normal limits in the majority of patients [9]. Consistent with these established features, the patients in our report presented with unremarkable tumor marker levels, reinforcing the diagnosis.

On imaging, HEHE typically presents as multifocal, often confluent nodules with a predilection for subcapsular locations. CT scans frequently show multiple low-density lesions accompanied by capsular retraction [1, 9]. Following contrast administration, lesions may show ring-like or peripheral enhancement during the arterial phase and a targetoid appearance in the portal venous phase [1, 6]. MRI characteristically shows HEHE lesions as heterogeneously hyperintense on T2-weighted sequences. A classic feature is a targetoid appearance, comprising a peripheral hyperintense rim (the ‘white ring’) and a markedly hyperintense center; post-contrast enhancement is often minimal [1, 7, 9, 10]. Although CT and MRI findings are suggestive, they are not specific; therefore, a definitive diagnosis of HEHE requires histopathological examination and immunohistochemical analysis.

Given the rarity and clinical heterogeneity of HEHE, standard-of-care treatment has not been established. Primary therapeutic strategies include liver transplantation, surgical resection, systemic chemotherapy, and interventional therapies [1, 11]. Liver transplantation is a principal treatment for multifocal HEHE, with reported overall survival rates of 90–100% at 1 year and 70–80% at 5 years [12, 13]. For unifocal, localized HEHE with an indolent course, surgical resection is the mainstay treatment, though it is associated with risks of postoperative complications and recurrence [9, 13]. Furthermore, its efficacy is limited in cases of multifocal or extrahepatic disease [6]. Although the clinical course of many HEHE patients is slow, those with pleural involvement or lymph node metastasis tend to have a poorer prognosis [1, 8].

With recent advances in image-guided thermal ablation, MWA has emerged as an effective and minimally invasive therapeutic option for patients with HEHE who are ineligible for surgical resection or liver transplantation, or for those who develop intrahepatic recurrence [1]. MWA is an ablative technique that utilizes high-frequency electromagnetic waves to generate thermal energy, thereby inducing coagulative necrosis of tumor tissue via localized hyperthermia. It offers the advantages of being a simple procedure with minimal trauma, rapid recovery, and high reproducibility [14, 15]. A multicenter retrospective study conducted by Zeng et al. [14] included 18 HEHE patients with 31 lesions who underwent image-guided thermal ablation. The median tumor size was 23.2 mm (range: 9–136 mm). With a median follow-up of 37.2 months, the 1-, 3-, and 5-year overall survival (OS) rates were 87.6%, 75.5%, and 75.5%, respectively; median OS was 90.5 months and median progression-free survival (PFS) was 23.8 months. Another study by Hu et al. [4] reported on six HEHE patients who underwent 16 sessions of image-guided hepatic ablation for 35 tumors with a mean size of 2.1 ± 1.3 cm. Their results showed that most lesions achieved a residual-free status during follow-up. Although local recurrence occurred in two patients, the lesions were successfully managed with repeat MWA, indicating its robust efficacy for both primary and recurrent disease. This suggests that a staged ablation approach may be a safer and more effective strategy for patients with multifocal disease [4]. Mechanistically, pre-ablation TACE decreases intratumoral perfusion, thereby reducing convective heat loss (“heat-sink”) and improving the completeness of the subsequent ablation zone. Devascularization may also promote tumor necrosis and lower intraprocedural bleeding risk, supporting a staged TACE plus MWA strategy for large lesions [16, 17]. A structured comparison of published outcomes is summarized in Table 2.

Table 2.

Structured comparison of published interventional and surgical outcomes in HEHE

Year (Refs.)	Population	Study design	Sample size	Endpoints	Key findings
2024 [13]	HEHE (ablation)	Multicenter retrospective	18 pts; 31 sessions	LTP; PFS/OS	LTP 6.5%; follow-up 37.2 mo (range 3–117); 5-year OS 75.5%.
2024 [4]	HEHE ( ablation)	Retrospective series	6 pts; 35 tumors	Local control; intrahepatic/distant progression	Local control 94.3% (33/35); imaging follow-up 43.0 ± 31.2 mo.
2020 [11]	HEHE (LT)	Registry cohort	131 listed; 88 LT	Post-LT survival	Post-LT 1/3/5-year OS: 88.6%/78.9%/77.2%.
2019 [12]	HEHE	Single-center retrospective	12	Treatment allocation patterns; survival/recurrence	Mixed strategies (LT/LR/RFA/observation); mean follow-up 39.6 ± 20.1 mo (range 15–82).
2025 [10]	HEHE (LT)	National registry analysis	121 LT	Post-LT survival	Post-LT survival comparable to other indications.

HEHE: hepatic epithelioid hemangioendothelioma; LT: liver transplantation; LR: liver resection; RFA: radiofrequency ablation; LTP: local tumor progression; PFS: progression-free survival; OS: overall survival

In our report, Case 1, who had multiple lesions, underwent two sessions of staged MWA. She experienced only minor peri-procedural complications which were resolved with conservative treatment. For Case 2, who presented with multiple lesions larger than 5 cm, some of which were confluent, we adopted a combination strategy of TACE followed by MWA. TACE involves the targeted delivery of chemotherapeutic agents to the tumor’s feeding arteries, followed by embolization with iodized oil and 100–300 μm bland microspheres. This obstructs the tumor’s blood supply, inducing ischemia, hypoxia, and subsequent necrosis [16, 17]. Clinical studies suggest that for liver tumors larger than 5 cm, combining TACE with MWA may enhance therapeutic efficacy by reducing tumor blood flow, thereby mitigating the “heat sink effect” that can limit the ablative zone [16, 18]. Case 2 received a total of one TACE procedure and four MWA sessions without any serious postoperative complications. Surveillance imaging with contrast-enhanced MRI demonstrated durable disease control over 40 and 84 months in Cases 1 and 2, respectively. While response was assessed primarily by serial contrast-enhanced MRI using mRECIST, response validation in HEHE may be strengthened by a more comprehensive imaging approach—multiparametric liver MRI with periodic extrahepatic surveillance (e.g., chest and/or whole-body CT), with FDG PET/CT considered as an adjunct when clinically indicated [1, 10].

This case report has some limitations, including generalizing efficacy or comparing strategies; therefore, the durable CR should be interpreted as a descriptive observation rather than evidence of causality. Response assessment is another key limitation: mRECIST was developed for hepatocellular carcinoma and has not been validated for HEHE, and post-treatment enhancement patterns in this rare vascular tumor can be heterogeneous, introducing potential uncertainty and the risk of misclassification (e.g., cystic change) when extrapolated to HEHE. Larger multicenter cohorts and prospective studies with standardized imaging protocols and response assessment are needed to define safety, durability, and patient selection for locoregional therapies in unresectable HEHE [19].

Beyond conventional clinicopathological and imaging evaluation, emerging computational modeling, artificial intelligence, and data-driven approaches are increasingly applied in oncology for risk stratification and treatment response prediction. Such methodologies may support individualized decision-making in rare malignancies like HEHE, where evidence remains limited. Integration of multiparametric imaging, clinical variables, and algorithm-based modeling could improve prognostic assessment and therapeutic planning. Further translational research incorporating advanced computational tools may enhance precision management of this rare vascular tumor [19–21].

Conclusions

While liver transplantation and surgical resection remain the standard therapeutic options for HEHE, our two cases suggest that MWA-based locoregional therapy—alone or in combination with TACE—may be a feasible option for selected patients with unresectable disease. Durable radiologic complete responses were observed after staged MWA for multifocal lesions and after TACE followed by MWA for a larger lesion. These findings warrant validation in larger multicenter studies to define safety, durability, and patient selection.

Author contributions

Jiapeng Sun and Chi Xu collected clinical data, reviewed the literature, and drafted the manuscript. Qiongyu Liang contributed to the literature review manuscript finalization. Kang Zhou and Jie Pan conceptualized the study, supervised the clinical management, and critically revised the manuscript. All authors read and approved the final manuscript.

Funding

This study received funding from the Peking Union Medical College Hospital Central High-Level Hospital Clinical Research Special Project (2022-PUMCH-B-069).

Data availability

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

Declarations

Ethics approval

The study protocol was approved by the Ethics Committee of Peking Union Medical College Hospital, in accordance with the principles of the Declaration of Helsinki (1975, as revised in 2008).

Consent to participate

Written informed consent was obtained from the patient for participation in this study.

Consent for publication

Written informed consent was obtained from the patients for publication of this case report and accompanying images.

Competing interests

The authors declare no competing interests.