Microwave Ablation and Transcatheter Arterial Chemoembolization for Hepatic Epithelioid Hemangioendothelioma Two Case Reports

Microwave Ablation and Transcatheter Arterial Chemoembolization for Hepatic Epithelioid Hemangioendothelioma Two Case Reports | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Microwave Ablation and Transcatheter Arterial Chemoembolization for Hepatic Epithelioid Hemangioendothelioma Two Case Reports Jiapeng Sun, Chi Xu, Qiongyu Liang, Kang Zhou, Jie Pan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7901075/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 16 You are reading this latest preprint version Abstract Background: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular sarcoma in which surgery or liver transplantation is often not feasible due to multifocal or unresectable disease. For these patients, standardized treatment protocols are lacking, and the long-term efficacy of non-surgical options has been limited. 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) and MWA combined with transcatheter arterial chemoembolization (TACE), highlighting their potential as durable treatment options for unresectable HEHE. Case Description: We describe two patients with pathologically confirmed, unresectable HEHE who achieved sustained complete response (CR). Case 1, a 47-year-old female with multifocal HEHE that had progressed despite prior systemic therapies, underwent staged MWA. After 40 months of follow-up, she maintained CR as assessed by mRECIST criteria. Case 2, a 53-year-old male, presented with multiple large and confluent lesions, the largest being 6.9 cm in diameter. He was treated with a combination of TACE and MWA. At an 84-month follow-up, he also remained in CR with significant tumor reduction and no signs of recurrence. Neither patient experienced serious treatment-related complications. Conclusions: For patients with unresectable HEHE, MWA appears to be a safe option that offers durable disease control. This report supports a staged MWA approach for multifocal lesions and a combined strategy with TACE for larger tumors. These findings highlight the emerging role of interventional therapies in the contemporary treatment paradigm of this rare hepatic sarcoma. Hepatic epithelioid hemangioendothelioma Microwave ablation Transcatheter arterial chemoembolization Interventional treatment Case report Figures Figure 1 Figure 2 Highlight box Key findings This study reports that minimally invasive interventional treatments achieved sustained CR in two patients with unresectable HEHE. Staged MWA for a patient with multifocal HEHE that had progressed despite prior systemic therapies resulted in CR maintained at 40-month follow-up. A combination of TACE and MWA for a patient presenting with multiple large and confluent lesions, the largest 6.9 cm, also led to CR maintained at 84-month follow-up, both assessed by mRECIST criteria. What is known and what is new? Surgery or liver transplantation is the primary therapy for HEHE but is often infeasible for patients with multifocal or unresectable disease; for these individuals, standardized non-surgical protocols with durable efficacy are lacking. This report provides critical long-term evidence (up to 84 months) demonstrating that MWA-based interventional therapies can provide safe and sustained disease control for unresectable HEHE. Its novelty lies in illustrating two distinct, effective strategies tailored to lesion characteristics: a staged MWA approach for multifocal disease and a TACE-MWA combination strategy for large, confluent lesions. What is the implication, and what should change now? For unresectable HEHE, interventional therapies—MWA alone or combined with TACE—should be considered primary treatment options for achieving long-term remission, rather than solely palliative. Staged MWA is effective for multifocal lesions, while TACE combined with MWA may improve outcomes in large tumors. 1. Introduction This manuscript is written following the CARE checklist. 1.1 Background Hepatic epithelioid hemangioendothelioma (HEHE) is a rare sarcoma of vascular origin, arising from vascular endothelial cells 1,2 . Surgical resection or liver transplantation is primary therapy for HEHE 1,3 . For patients with multiple HEHE that is unresectable or ineligible for liver transplantation, alternative treatments such as irreversible electroporation, radiofrequency ablation, and adjuvant chemotherapy may be considered. However, their long-term efficacy remains limited 1,4 . 1.2 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 studies clinically. 1.3 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. 2. Case Presentation All patient data have been de-identified, and written informed consent was obtained from both individuals. 2.1 Case 1 A 47-year-old woman with no significant medical or infectious disease history was found with hepatic lesions incidentally 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. 1 A). In the portal venous phase, contrast-enhanced images demonstrated lesions with peripheral and central hypoenhancement, separated by an intermediate enhancing band (Fig. 1 B). Laboratory tests, including tumor markers, were within normal limits. 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 the progression despite targeted therapy, MWA was initiated. 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 minutes (Fig. 1 C–E). Post-procedure, the patient experienced mild anemia and lumbar discomfort, both managed conservatively. A second MWA session was performed on October 28, 2021, using two probes and six ablation sites at 40–50 W for 30 minutes (Fig. 1 H). The patient recovered without complications. At 40-month follow-up, contrast-enhanced MRI showed post-ablation changes without evidence of residual or recurrent disease, consistent with a complete response (CR) according to mRECIST criteria (Fig. 1 I, J). 2.2 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. 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. Embolization was performed with 3.5 mL of iodized oil followed by 100–300 µm bland microspheres (Fig. 2 E–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 minutes (Fig. 2 I, J). The remaining lesions were subsequently treated over three additional MWA sessions, as detailed in Table 1 . Follow-up MRI demonstrated a significant reduction in the lesion size, with stable post-ablation changes and no evidence of tumor viability. This outcome was classified as CR according to mRECIST criteria (Fig. 2 K and L). After a follow-up period of 84 months, the lesions remained stable with no signs of recurrence. Table 1 Tumor Information and Treatment Outcomes Patient number 1 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 Treatments 3 5 Treatment Modality MWA TACE + MWA Follow-up Duration (months) 40 84 mRECIST CR CR mRECIST CR CR a Tumor diameter presented as median (range). CR: complete response 3. Discussion HEHE is a rare vascular sarcoma of low-grade malignancy, with an annual incidence of less than one case per million population. The disease has a higher incidence in females than in males 1 , 2 , 5 . Clinically, HEHE typically presents 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 , 5 , 6 . 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 5 , 7 . 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 8 . 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 , 8 . 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 , 5 .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 , 6 , 8 , 9 . 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 , 10 . 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 11 , 12 . 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 8 , 12 . Furthermore, its efficacy is limited in cases of multifocal or extrahepatic disease 5 . 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 , 7 . 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 13 , 14 . A multicenter retrospective study conducted by Zeng et al. 13 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 In our report, Case 1, who had multiple lesions, underwent three sessions of staged MWA. She experienced only minor peri-procedural complications, including fever and abdominal distension, which 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 15 , 16 . 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 15 , 17 . Case 2 received a total of one TACE procedures and four MWA sessions without any serious postoperative complications. During their postoperative follow-up, both patients underwent contrast-enhanced abdominal MRI every three months for the first year to assess treatment response and monitor for residual or new lesions, followed by MRI every six months combined with chest CT for comprehensive evaluation. At the time of this report, the patients have been followed for 40 and 84 months, respectively. In Case 1, who received staged MWA sessions, follow-up MRI showed cystic changes within the lesions without any signs of enhancement. Although the lesion volume did not significantly decrease, these cystic changes are consistent with post-ablation liquefaction necrosis, not residual viable tumor. In Case 2, who received combination therapy, follow-up MRI revealed a significant reduction in lesion volume with no signs of activity. This suggests that the addition of TACE may have contributed to a more robust radiological response, particularly when managing large or confluent lesions. 4. Conclusions While liver transplantation and surgical resection remain the standard of care for HEHE, our findings suggest that interventional treatment represents a valuable alternative for patients with unresectable HEHE. This report demonstrates that staged MWA, alone or in combination with TACE, can achieve sustained complete response and long-term survival in patients with multifocal HEHE. These minimally invasive strategies represent effective treatment options in the management of this rare vascular sarcoma. Declarations Ethical 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 participate for this study. Consent to publish: Written informed consent was obtained from the patient for publication of this case report and accompanying images. 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 statement: No datasets were generated or analyzed for this case report. All relevant clinical information is included within the article. Author Contribution 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 of the final manuscript. Acknowledgments We sincerely acknowledge the patient for providing consent and allowing us to share this case to contribute to clinical knowledge and future patient care, and funding from Peking Union Medical College Hospital. Data Availability No datasets were generated or analyzed for this case report. All relevant clinical information is included within the article. References Stacchiotti S, Miah AB, Frezza AM, et al. Epithelioid hemangioendothelioma, an ultra-rare cancer: a consensus paper from the community of experts. ESMO Open. 2021;6(3):100170. 10.1016/j.esmoop.2021.100170 . Choi KH, Moon WS. Epithelioid hemangioendothelioma of the liver. Clin Mol Hepatol. 2013;19(3):315–9. 10.3350/cmh.2013.19.3.315 . Lai Q, Feys E, Karam V, et al. Hepatic epithelioid hemangioendothelioma and adult liver transplantation: proposal for a prognostic score based on the analysis of the ELTR-ELITA registry. Transplantation. 2017;101(3):555–64. 10.1097/TP.0000000000001603 . Hu EY, Bhagavatula SK, Shi A, Merriam P, Levesque VM, Shyn PB. Image-guided percutaneous ablation of hepatic epithelioid hemangioendothelioma. Abdom Radiol. 2024;49(4):1241–7. 10.1007/s00261-023-04154-y . Ajay PS, Tsagkalidis V, Casabianca A, et al. A review of hepatic epithelioid hemangioendothelioma—Analyzing patient characteristics and treatment strategies. J Surg Oncol. 2022;126(8):1423–9. 10.1002/jso.27066 . Guo Q, Xue J, Xu L, Shi Z, Zhou B. The clinical features of epithelioid hemangioendothelioma in a Han Chinese population. Med (Baltim). 2017;96(26):e7345. 10.1097/MD.0000000000007345 . Rosenbaum E, Jadeja B, Xu B, et al. Prognostic stratification of clinical and molecular epithelioid hemangioendothelioma subsets. Mod Pathol. 2020;33(4):591–602. 10.1038/s41379-019-0368-8 . Wu X, Li B, Zheng C, Hong T, He X. Clinical characteristics of epithelioid hemangioendothelioma: a single-center retrospective study. Eur J Med Res. 2019;24(1):16. 10.1186/s40001-019-0375-8 . Ganeshan D, Pickhardt PJ, Morani AC, et al. Hepatic hemangioendothelioma: CT, MR, and FDG-PET-CT in 67 patients—a bi-institutional comprehensive cancer center review. Eur Radiol. 2020;30(5):2435–42. 10.1007/s00330-019-06637-3 . Larson EL, Ciftci Y, Jenkins RT, Zhou AL, Ruck JM, Philosophe B. Outcomes of liver transplant for hepatic epithelioid hemangioendothelioma. Clin Transpl. 2025;39(2):e70087. 10.1111/ctr.70087 . Brahmbhatt M, Prenner S, Bittermann T. Liver Transplantation for Hepatic Epithelioid Hemangioendothelioma Is Facilitated by Exception Points With Acceptable Long-term Outcomes. Transplantation. 2020;104(6):1187–92. 10.1097/TP.0000000000002982 . Cao L, Hong J, Zhou L, et al. Selection of treatment for hepatic epithelioid hemangioendothelioma: a single-center experience. World J Surg Oncol. 2019;17(1):183. 10.1186/s12957-019-1729-y . Zeng Q, Luo Y, Yu J, et al. Image-Guided Thermal Ablation for Hepatic Epithelioid Hemangioendothelioma: A Multicenter Experience. J Vasc Interv Radiol. 2024;35(7):1004–11. 10.1016/j.jvir.2024.03.023 . Ceppa EP, Collings AT, Abdalla M, et al. SAGES/AHPBA guidelines for the use of microwave and radiofrequency liver ablation for the surgical treatment of hepatocellular carcinoma or colorectal liver metastases less than 5 cm. Surg Endosc. 2023;37(12):8991–9000. 10.1007/s00464-023-10468-1 . Floridi C, Cacioppa LM, Rossini N, et al. Microwave ablation followed by cTACE in 5-cm HCC lesions: does a single-session approach affect liver function? Radiol Med (Torino). 2024;129(8):1252–64. 10.1007/s11547-024-01842-7 . Zhu Z yi, Yuan M, Yang PP et al. Single medium-sized hepatocellular carcinoma treated with sequential conventional transarterial chemoembolization (cTACE) and microwave ablation at 4 weeks versus cTACE alone: a propensity score. World J Surg Oncol . 2022;20(1):192. 10.1186/s12957-022-02643-w Jing C, Li J, Yuan C, et al. Therapeutic analysis of 632 cases treated by transcatheter arterial chemoembolization combined with ablation in hepatocellular carcinoma: A retrospective study. Eur J Radiol. 2024;178:111619. 10.1016/j.ejrad.2024.111619 . Additional Declarations No competing interests reported. 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14:00:44","extension":"html","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":69686,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7901075/v1/3ff77ace25ed343362e7421f.html"},{"id":97261067,"identity":"b6dafc92-3915-4942-9052-a312166e407b","added_by":"auto","created_at":"2025-12-02 14:00:44","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":131481,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCase 1, a 47-year-old female treated with staged MWA\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA and 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 and 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 and 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 and 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.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7901075/v1/467d04fa1b178cf3bd486057.jpg"},{"id":97367614,"identity":"331fb508-b0df-43ea-b974-4cc037fe3192","added_by":"auto","created_at":"2025-12-03 16:19:48","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":199789,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCase 2, a 53-year-old male treated with TACE combined with MWA\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA and 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 and 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 and J: A dual-probe MWA was performed to ablate the multiple lesions in the right lobe. K and L: An 84-month follow-up contrast-enhanced MRI shows a significant reduction in lesion size, indicating successful coagulative necrosis.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7901075/v1/06f5035bbb8130a5d39f372f.jpg"},{"id":97372735,"identity":"28ddd3c0-bfc0-4ebc-b366-07a30220d842","added_by":"auto","created_at":"2025-12-03 16:33:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":812853,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7901075/v1/fe5620eb-e3f2-4249-b18c-97296696e850.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Microwave Ablation and Transcatheter Arterial Chemoembolization for Hepatic Epithelioid Hemangioendothelioma Two Case Reports","fulltext":[{"header":"Highlight box ","content":"\u003cp\u003e\u003cstrong\u003eKey findings\u003c/strong\u003e\u003c/p\u003e\n\u003cul start=\"50\"\u003e\n \u003cli\u003eThis study reports that minimally invasive interventional treatments achieved sustained CR in two patients with unresectable HEHE. Staged MWA for a patient with multifocal HEHE that had progressed despite prior systemic therapies resulted in CR maintained at 40-month follow-up. A combination of TACE and MWA for a patient presenting with multiple large and confluent lesions, the largest 6.9 cm, also led to CR maintained at 84-month follow-up, both assessed by mRECIST criteria.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eWhat is known and what is new?\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cul start=\"50\"\u003e\n \u003cli\u003eSurgery or liver transplantation is the primary therapy for HEHE but is often infeasible for patients with multifocal or unresectable disease; for these individuals, standardized non-surgical protocols with durable efficacy are lacking.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eThis report provides critical long-term evidence (up to 84 months) demonstrating that MWA-based interventional therapies can provide safe and sustained disease control for unresectable HEHE. Its novelty lies in illustrating two distinct, effective strategies tailored to lesion characteristics: a staged MWA approach for multifocal disease and a TACE-MWA combination strategy for large, confluent lesions.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eWhat is the implication, and what should change now?\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cul start=\"50\"\u003e\n \u003cli\u003eFor unresectable HEHE, interventional therapies\u0026mdash;MWA alone or combined with TACE\u0026mdash;should be considered primary treatment options for achieving long-term remission, rather than solely palliative. Staged MWA is effective for multifocal lesions, while TACE combined with MWA may improve outcomes in large tumors.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"1. Introduction","content":"\u003cp\u003eThis manuscript is written following the CARE checklist.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.1 Background\u003c/p\u003e\n\u003cp\u003eHepatic epithelioid hemangioendothelioma (HEHE) is a rare sarcoma of vascular origin, arising from vascular endothelial cells\u003csup\u003e1,2\u003c/sup\u003e. Surgical resection or liver transplantation is primary therapy for HEHE\u003csup\u003e1,3\u003c/sup\u003e. For patients with multiple HEHE that is unresectable or ineligible for liver transplantation, alternative treatments such as irreversible electroporation, radiofrequency ablation, and adjuvant chemotherapy may be considered. However, their long-term efficacy remains limited\u003csup\u003e1,4\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e1.2 Rationale and Knowledge Gap\u003c/p\u003e\n\u003cp\u003eGiven 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 studies clinically.\u003c/p\u003e\n\u003cp\u003e1.3 Objective\u003c/p\u003e\n\u003cp\u003eThis 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.\u003c/p\u003e"},{"header":"2. Case Presentation","content":"\u003cp\u003e All patient data have been de-identified, and written informed consent was obtained from both individuals.\u003c/p\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Case 1\u003c/h2\u003e\u003cp\u003eA 47-year-old woman with no significant medical or infectious disease history was found with hepatic lesions incidentally during a routine ultrasound on April 20, 2021. Abdominal magnetic resonance imaging (MRI) revealed multiple ovoid intrahepatic lesions. The largest measured approximately 4.5 \u0026times; 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.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). In the portal venous phase, contrast-enhanced images demonstrated lesions with peripheral and central hypoenhancement, separated by an intermediate enhancing band (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). Laboratory tests, including tumor markers, were within normal limits.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eA 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.\u003c/p\u003e\u003cp\u003eGiven her ineligibility for surgical resection and the progression despite targeted therapy, MWA was initiated. 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 \u0026times; 3.0 cm and 2.1 \u0026times; 1.8 cm, respectively. The procedure involved six ablation sites at 50 W for a total of 30 minutes (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC\u0026ndash;E). Post-procedure, the patient experienced mild anemia and lumbar discomfort, both managed conservatively. A second MWA session was performed on October 28, 2021, using two probes and six ablation sites at 40\u0026ndash;50 W for 30 minutes (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eH). The patient recovered without complications. At 40-month follow-up, contrast-enhanced MRI showed post-ablation changes without evidence of residual or recurrent disease, consistent with a complete response (CR) according to mRECIST criteria (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eI, J).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Case 2\u003c/h2\u003e\u003cp\u003eA 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\u0026ndash;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.\u003c/p\u003e\u003cp\u003eOn November 27, 2017, the patient received TACE combined with MWA. 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. Embolization was performed with 3.5 mL of iodized oil followed by 100\u0026ndash;300 \u0026micro;m bland microspheres (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eE\u0026ndash;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\u0026ndash;50 W for a total of 28 minutes (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eI, J).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe remaining lesions were subsequently treated over three additional MWA sessions, as detailed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Follow-up MRI demonstrated a significant reduction in the lesion size, with stable post-ablation changes and no evidence of tumor viability. This outcome was classified as CR according to mRECIST criteria (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eK and L). After a follow-up period of 84 months, the lesions remained stable with no signs of recurrence.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eTumor Information and Treatment Outcomes\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatient number\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge(years)/Sex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e47/Female\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e53/Male\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of Tumors\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor Diameter (cm)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.0 (2.1\u0026ndash;4.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.9 (2.3\u0026ndash;6.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of Treatments\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTreatment Modality\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMWA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTACE\u0026thinsp;+\u0026thinsp;MWA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFollow-up Duration (months)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e84\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emRECIST\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCR\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emRECIST\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCR\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003csup\u003ea\u003c/sup\u003eTumor diameter presented as median (range).\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003eCR: complete response\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Discussion","content":"\u003cp\u003eHEHE is a rare vascular sarcoma of low-grade malignancy, with an annual incidence of less than one case per million population. The disease has a higher incidence in females than in males\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Clinically, HEHE typically presents 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\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. 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\u0026mdash;including those in this report\u0026mdash;may be entirely asymptomatic at diagnosis\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. 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\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. 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\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Consistent with these established features, the patients in our report presented with unremarkable tumor marker levels, reinforcing the diagnosis.\u003c/p\u003e\u003cp\u003eOn 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\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Following contrast administration, lesions may show ring-like or peripheral enhancement during the arterial phase and a targetoid appearance in the portal venous phase\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.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 \u0026lsquo;white ring\u0026rsquo;) and a markedly hyperintense center; post-contrast enhancement is often minimal\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Although CT and MRI findings are suggestive, they are not specific; therefore, a definitive diagnosis of HEHE requires histopathological examination and immunohistochemical analysis.\u003c/p\u003e\u003cp\u003eGiven 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\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Liver transplantation is a principal treatment for multifocal HEHE, with reported overall survival rates of 90%\u0026ndash;100% at 1 year and 70%\u0026ndash;80% at 5 years\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. 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\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Furthermore, its efficacy is limited in cases of multifocal or extrahepatic disease\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Although the clinical course of many HEHE patients is slow, those with pleural involvement or lymph node metastasis tend to have a poorer prognosis\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eWith 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\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. 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\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. A multicenter retrospective study conducted by Zeng et al.\u003csup\u003e13\u003c/sup\u003e included 18 HEHE patients with 31 lesions who underwent image-guided thermal ablation. The median tumor size was 23.2 mm (range: 9\u0026ndash;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.\u003csup\u003e4\u003c/sup\u003e reported on six HEHE patients who underwent 16 sessions of image-guided hepatic ablation for 35 tumors with a mean size of 2.1\u0026thinsp;\u0026plusmn;\u0026thinsp;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.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eIn our report, Case 1, who had multiple lesions, underwent three sessions of staged MWA. She experienced only minor peri-procedural complications, including fever and abdominal distension, which 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\u0026ndash;300 \u0026micro;m bland microspheres. This obstructs the tumor's blood supply, inducing ischemia, hypoxia, and subsequent necrosis\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. 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\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. Case 2 received a total of one TACE procedures and four MWA sessions without any serious postoperative complications. During their postoperative follow-up, both patients underwent contrast-enhanced abdominal MRI every three months for the first year to assess treatment response and monitor for residual or new lesions, followed by MRI every six months combined with chest CT for comprehensive evaluation. At the time of this report, the patients have been followed for 40 and 84 months, respectively. In Case 1, who received staged MWA sessions, follow-up MRI showed cystic changes within the lesions without any signs of enhancement. Although the lesion volume did not significantly decrease, these cystic changes are consistent with post-ablation liquefaction necrosis, not residual viable tumor. In Case 2, who received combination therapy, follow-up MRI revealed a significant reduction in lesion volume with no signs of activity. This suggests that the addition of TACE may have contributed to a more robust radiological response, particularly when managing large or confluent lesions.\u003c/p\u003e"},{"header":"4. Conclusions","content":"\u003cp\u003eWhile liver transplantation and surgical resection remain the standard of care for HEHE, our findings suggest that interventional treatment represents a valuable alternative for patients with unresectable HEHE. This report demonstrates that staged MWA, alone or in combination with TACE, can achieve sustained complete response and long-term survival in patients with multifocal HEHE. These minimally invasive strategies represent effective treatment options in the management of this rare vascular sarcoma.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval:\u003c/strong\u003e\u003cp\u003eThe 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).\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConsent to participate:\u003c/strong\u003e\u003cp\u003e Written informed consent was obtained from the patient for participate for this study.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConsent to publish:\u003c/strong\u003e\u003cp\u003e Written informed consent was obtained from the patient for publication of this case report and accompanying images.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e\u003cp\u003eThis study received funding from the Peking Union Medical College Hospital Central High-Level Hospital Clinical Research Special Project (2022-PUMCH-B-069).\u003c/p\u003e\u003cp\u003eData availability statement: No datasets were generated or analyzed for this case report. All relevant clinical information is included within the article.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eContributions: 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 of the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e\u003cp\u003eWe sincerely acknowledge the patient for providing consent and allowing us to share this case to contribute to clinical knowledge and future patient care, and funding from Peking Union Medical College Hospital.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eNo datasets were generated or analyzed for this case report. All relevant clinical information is included within the article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eStacchiotti S, Miah AB, Frezza AM, et al. Epithelioid hemangioendothelioma, an ultra-rare cancer: a consensus paper from the community of experts. ESMO Open. 2021;6(3):100170. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.esmoop.2021.100170\u003c/span\u003e\u003cspan address=\"10.1016/j.esmoop.2021.100170\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChoi KH, Moon WS. Epithelioid hemangioendothelioma of the liver. 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Eur J Radiol. 2024;178:111619. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ejrad.2024.111619\u003c/span\u003e\u003cspan address=\"10.1016/j.ejrad.2024.111619\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Hepatic epithelioid hemangioendothelioma, Microwave ablation, Transcatheter arterial chemoembolization, Interventional treatment, Case report","lastPublishedDoi":"10.21203/rs.3.rs-7901075/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7901075/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground:\u003c/p\u003e\n\u003cp\u003eHepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular sarcoma in which surgery or liver transplantation is often not feasible due to multifocal or unresectable disease. For these patients, standardized treatment protocols are lacking, and the long-term efficacy of non-surgical options has been limited. 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) and MWA combined with transcatheter arterial chemoembolization (TACE), highlighting their potential as durable treatment options for unresectable HEHE.\u003c/p\u003e\n\u003cp\u003eCase Description:\u003c/p\u003e\n\u003cp\u003eWe describe two patients with pathologically confirmed, unresectable HEHE who achieved sustained complete response (CR). Case 1, a 47-year-old female with multifocal HEHE that had progressed despite prior systemic therapies, underwent staged MWA. After 40 months of follow-up, she maintained CR as assessed by mRECIST criteria. Case 2, a 53-year-old male, presented with multiple large and confluent lesions, the largest being 6.9 cm in diameter. He was treated with a combination of TACE and MWA. At an 84-month follow-up, he also remained in CR with significant tumor reduction and no signs of recurrence. Neither patient experienced serious treatment-related complications.\u003c/p\u003e\n\u003cp\u003eConclusions:\u003c/p\u003e\n\u003cp\u003eFor patients with unresectable HEHE, MWA appears to be a safe option that offers durable disease control. This report supports a staged MWA approach for multifocal lesions and a combined strategy with TACE for larger tumors. These findings highlight the emerging role of interventional therapies in the contemporary treatment paradigm of this rare hepatic sarcoma.\u003c/p\u003e","manuscriptTitle":"Microwave Ablation and Transcatheter Arterial Chemoembolization for Hepatic Epithelioid Hemangioendothelioma Two Case Reports","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-02 14:00:39","doi":"10.21203/rs.3.rs-7901075/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-20T13:50:48+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-11T03:06:59+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-07T15:30:46+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-01T10:44:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"97501424000032880909322120157848006774","date":"2025-12-29T14:41:03+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-28T14:36:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"216001808651637417694622850719804450285","date":"2025-12-26T12:22:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"19332004965415265879690697169271143256","date":"2025-12-26T09:31:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"144999193479279629525085232870596624757","date":"2025-12-26T07:44:51+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-27T19:47:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"39845873315327144213169118251498360825","date":"2025-11-27T19:06:54+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-26T11:59:44+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-11-25T11:34:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-11T10:01:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-11T06:54:23+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Oncology","date":"2025-11-11T06:51:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"64f7ebd0-b717-4fe3-bed9-885fbbf7b013","owner":[],"postedDate":"December 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-24T16:11:31+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-02 14:00:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7901075","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7901075","identity":"rs-7901075","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}