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Holly Barker
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Abdelmogod, A.; Papadopoulos, L.; Riordan, S.; Wong, M.; Weltman, M.; Lim, R.; Mcevoy, C.; Fellowes, A.; Fox, S.; Bedő, J.; et al. Epithelioid Haemangioendothelioma. Encyclopedia. Available online: https://encyclopedia.pub/entry/50160 (accessed on 02 August 2024).
Abdelmogod A, Papadopoulos L, Riordan S, Wong M, Weltman M, Lim R, et al. Epithelioid Haemangioendothelioma. Encyclopedia. Available at: https://encyclopedia.pub/entry/50160. Accessed August 02, 2024.
Abdelmogod, Arwa, Lia Papadopoulos, Stephen Riordan, Melvin Wong, Martin Weltman, Ratana Lim, Christopher Mcevoy, Andrew Fellowes, Stephen Fox, Justin Bedő, et al. "Epithelioid Haemangioendothelioma" Encyclopedia, https://encyclopedia.pub/entry/50160 (accessed August 02, 2024).
Abdelmogod, A., Papadopoulos, L., Riordan, S., Wong, M., Weltman, M., Lim, R., Mcevoy, C., Fellowes, A., Fox, S., Bedő, J., Penington, J., Pham, K., Hofmann, O., Vissers, J.H.A., Grimmond, S., Ratnayake, G., Christie, M., Mitchell, C., Murray, W.K., ...Barker, H.E.. (2023, October 12). Epithelioid Haemangioendothelioma. In Encyclopedia. https://encyclopedia.pub/entry/50160
Abdelmogod, Arwa, et al. "Epithelioid Haemangioendothelioma." Encyclopedia. Web. 12 October, 2023.
Epithelioid Haemangioendothelioma
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This entry is adapted from the peer-reviewed paper 10.3390/cancers15174378

Epithelioid haemangioendothelioma (EHE) is an ultra-rare malignant vascular tumour with a prevalence of 1 per 1,000,000. It develops from endothelial cells, which are the cells that line all blood vessels in the body. Therefore, it typically expresses endothelial cell markers. It can also be identified through analysis of the genes. Two genes, WWTR1 and CAMTA1, are broken and fused together in 90% of cases. Alternatively, in approximately 10% of cases, the genes that are broken and fused together are YAP1 and TFE3. 

epithelioid haemangioendothelioma rare cancer malignant vascular tumour

1. Introduction

Epithelioid haemangioendothelioma (EHE) is a rare, low-to-intermediate grade malignant tumour of vascular origin that may develop in the extremities, soft tissue, lung, bone, and liver. The name was first coined in 1982 by Weiss and Enzinger due to its overlapping features between a haemangioma and angiosarcoma. It is a very rare tumour with a prevalence of 1 per 1,000,000 in the general population [1].
The World Health Organisation (WHO) has recommended that EHE be grouped with malignant tumours [2]. It has an unpredictable clinical behaviour ranging from indolent to aggressively malignant, with a mean survival of 4.6 years, ranging from 6 months to 24 years [2]. Risk stratification models have been proposed to identify lesions at high risk for tumour progression, with tumour cellularity, tumour size, high mitotic figures, and a Ki67 score greater than 10% being the most significant indicators for poor prognosis [3][4].
EHE has no standard treatment regimen, and very few therapeutic options are available. Historically, liver resection and transplantation has been the only curative option for patients with hepatic EHE because of tumour multifocality, but is associated with variable outcomes [5]. However, an expanding oncology therapeutic landscape and advances in genomic tumour analysis may help direct the choice of potentially active treatments, such as those targeting vascular endothelial growth factor (VEGF) or immunotherapy.

2. Epithelioid Haemangioendothelioma 

2.1. Radiological Characterisation

Radiologic findings are often nonspecific and vary according to the site. Two characteristic computed tomography (CT) and magnetic resonance imaging (MRI) findings in hepatic EHE include the “lollipop sign”, in larger lesions (>5 cm) due to bridging vein thrombosis with a rounded “head” and a tapering “tail” [6], and the “target sign”, which is a lesion with a low intensity central area surrounded by a hyperintense rim, and is more likely to be found in smaller lesions (2–5 cm) [7]. Of note, benign-looking pulmonary calcification and hepatic capsular retractions are common findings in positron-emission topography (PET)/CT scans of pleural and hepatic EHE, respectively [8].

2.2. Histopathological Features

Morphologically, EHE is most often composed of epithelioid cells, organised in nests or cords, with eosinophilic to vacuolated cytoplasm, set in a distinctive myxohyaline stroma, and occasionally associated with haemorrhagic foci [9]. Blister cells with intraluminal erythrocytes, mild-to-moderate atypia, and a low rate of mitosis may also be present [10]. Immunohistochemical (IHC) stains show EHE consistently expresses endothelial cell markers (CD31, CD34 and ERG), and up to 40% of cases may be positive for cytokeratins [11]. EHE with a YAP1::TFE3 fusion has several distinct morphologic features, including voluminous cytoplasm, well-formed vascular lumens, solid growth, and minimal or no stroma [10]. A minority of cases show atypical or malignant features, such as increased cytological atypia and increased mitotic activity with or without necrosis, and may have morphologic overlap with epithelioid angiosarcoma [12].

2.3. Molecular Characterisation

The WHO classification of sarcomas and the European Society of Medical Oncology (ESMO) consensus have set two gene translocations, both involving the Hippo pathway, as disease-defining fusion genes for EHE [13][14]. The Hippo pathway is involved in normal development, cell growth and homeostasis, hence its dysfunction can lead to the development and progression of multiple cancers [15][16]. The pathognomonic WWTR1::CAMTA1 fusion, which results from a t(1;3)(p36.3;q25) translocation, and the less common YAP1::TFE3 fusion are considered diagnostic fusion genes [13][14][17]. Most cases of EHE are characterised by WWTR1::CAMTA1 (90%) or YAP1::TFE3 (10%) gene fusions [14].
Transcriptional co-activator with PDZ-binding motif (TAZ), encoded by the WWTR1 gene, regulates the activity of various transcription factors, including the Transcriptional enhancer associated domain (TEAD) transcription factors, which play roles in cell proliferation and apoptosis [18]. Nuclear translocation of TAZ is inhibited by upstream proteins in the Hippo pathway [18]. The fusion between TAZ and CAMTA1 results in constitutive activation of TAZ, hyperactivation of TEAD-based transcriptional programs, and upregulated cellular proliferation [19][20] which may be inhibited with drugs that modulate TEAD activity [21].
YAP1 is a transcriptional coactivator, also controlled by the Hippo signalling pathway, which also interacts with transcription factors, such as TEADs, to promote growth and inhibit apoptosis [18]. TFE3 belongs to the MiTF/TFE family of basic helix-loop-helix (bHLH) transcription factors and regulates lysosomal biogenesis and energy homeostasis [22]. The YAP1::TFE3 fusion protein also drives hyperactivation of TEAD-based transcription programs [19].
These different fusion genes give rise to diverse biologic behaviour. Some propose that YAP1-TFE3 fusion tumours should be classified as a distinct entity given their unique clinical and histopathologic characteristics in comparison to conventional EHE [9][23]. In addition, YAP1::TFE3 fused EHE tends to arise in younger patients and has a more favourable outcome than EHE characterised by TAZ::CAMTA1 fusions, with the 5-year overall survival being 86% versus 59%, respectively [23][24].
Next-generation DNA sequencing (IMPACT) and targeted RNA sequencing (Archer FusionPlex Custom Solid Panel) on cohorts of 18 and 49 patients have uncovered additional drivers; at least 22% of cases had alterations in cell cycle and epigenetic pathways, and/or loss-of-function alterations in the DNA damage response pathways. These included pathogenic variants in XRCC1/2, ERCC1, RB1, APC, FANCA, CDKN2A and CKDN2B and ATRX loss [25]. More than 50% of EHE tumours have secondary genomic variants, the presence of which may indicate more aggressive disease [24].

2.4. Clinical Behaviour

Notably, EHE has a variable clinical behaviour: patients with either solitary soft tissue or multifocal lung/liver disease may follow a relatively indolent course, whereas those with either pleural or lymph node involvement, regardless of their primary site or pathologic grade, follow a highly aggressive clinical course similar to a high-grade sarcoma [24]. In general, Mehrabi et al. found that the 1-, 3-, and 5-year survival rates for hepatic EHE, regardless of treatment, were 83.4%, 55.7% and 41.1%, respectively [5].
Several sets of predictors of clinical outcomes have been proposed. Clinical factors associated with shorter survival include: clinical baseline tumour-related pain (TRP), development of TRP during follow-up, baseline temperature, and development of fatigue during follow-up [26]; multifocality, nodal involvement, lung primary, and distant metastasis [24][27]. A proposed three-tiered risk assessment system using tumour size and histologic atypia (defined as high mitotic rate, tumour grade and coagulative necrosis) to stratify patients into low-risk, intermediate-risk, and high-risk groups has shown 5-year overall survival rates of 100%, 81.8%, and 16.9%, respectively [28]. Most recently, Li et al. have established and internally validated the first EHE nomogram prognostic model [29]. Based on the Surveillance, Epidemiology, and End Results (SEER) database, they recruited 512 EHE patients and calculated overall survival (OS) at 1, 5, and 10 years for all patients as 76.5%, 57.4%, and 48.2%, respectively. The age, tumour stage, degree of tissue differentiation, surgical treatment, chemotherapy, and radiotherapy were independent factors predicting prognosis [29].

2.5. Treatment and Management Principles

There is no universally agreed treatment strategy for EHE due to its rarity and lack of comprehensive molecular characterisation. However, a recent consensus strategy by experts and consumers has been published.
Treatment strategies include liver transplantation (44.8%), surgical resection for isolated tumours (9.4%) [14][30][31][32], and chemotherapy [5]. Although active surveillance has never been formally studied, it is also a common practice in experienced centres, particularly for a favourable prognostic subgroup [24]. Indeed, active surveillance is the preferred upfront approach in asymptomatic patients (level of evidence V, B) by the ESMO and SPAEN (Sarcoma Patient EuroNet) [14][33].
Based on analysis of the World Sarcoma Network database, all systemic treatments for sarcoma have limited activity in EHE. Seventy-three patients (33 treated with anthracycline-based regimens, 11 with weekly paclitaxel, 12 with pazopanib, 15 with IFN-α 2b and 27 with other agents) were included, and none showed meaningful activity [34]. Systemic therapy should be reserved for patients with unresectable disease which is symptomatic and progressive. By contrast the experience with targeted therapies (Table 1), especially with VEGF(R) inhibitors and mTOR inhibitors, is slightly more encouraging, with the potential advantage of a more favourable toxicity profile. In particular, VEGF inhibition with bevacizumab is a promising therapy that exploits the vascular nature of EHE and is well tolerated [35][36].
There are currently no reported cases of delivering genomically guided therapies against any of the identified molecular targets. However, novel small molecules targeting the Hippo pathway are in early-phase trials (NCT04665206) [37]. The fusions identified in EHE are also thought to lead to activation of the MEK signalling pathway. Based on this, trametinib is under investigation in an ongoing phase II clinical trial (NCT03148275) [38].
Table 1. Targeted Therapies in EHE.
Treatment
[Reference]		 Study Design and Patient Nos. Study Outcome [CR, PR, SD, PD]
Sirolimus
[39]		 A case-series analysis within the Italian Rare Cancer Network for 38 EHE patients
  • 4 PR (10.8%)
  • 28 SD (75.7%)
  • 5 PD (13.5%)
Pazopanib
[40]		 A retrospective analysis; an EORTC of Soft tissue and Bone Sarcoma group of 10 EHE patients
  • 1 (10%) CR
  • 1 (10%) PR
  • 4 (40%) SD
  • 3 (30%) PD
  • 1 (10%) unknown
Bevacizumab
[35]		 A multicentre, phase II study with 7 EHE patients
  • 2 PR (29%)
  • 4 SD (57%)
  • 1 PD (14%)
[36] Case series of 4 EHE patients
  • 3 PR to paclitaxel and bevacizumab.
  • 1 SD on bevacizumab
[41] Case report of one EHE patient 1 PR to capecitabine and bevacizumb for 6 months.
Sorafenib
[42]		 Phase II study by the French Sarcoma Group of 15 EHE patients
  • 2 PR lasting 2 and 9 months
  • Non-progression rate of 6 patients (46.5%) at 4 months and 5 patients (38.4%) at 6 months.
Lenalidomide
[43]		 A case report of one EHE patient
  • SD 39 months
On treatment discontinuation, slight progression seen, responded to rechallenge.
Anlotinib
[44]		 A case report of one EHE patient SD for more than 2 years
Lenvatinib
[45]		 A case report of one EHE patient PR for 6 months bridging liver transplant

References

  1. Weiss, S.W.; Enzinger, F.M. Epithelioid hemangioendothelioma: A vascular tumor often mistaken for a carcinoma. Cancer 1982, 50, 970–981.
  2. Sardaro, A.; Bardoscia, L.; Petruzzelli, M.F.; Portaluri, M. Epithelioid hemangioendothelioma: An overview and update on a rare vascular tumor. Oncol. Rev. 2014, 8, 259.
  3. Deyrup, A.T.; Tighiouart, M.; Montag, A.G.; Weiss, S.W. Epithelioid hemangioendothelioma of soft tissue: A proposal for risk stratification based on 49 cases. Am. J. Surg. Pathol. 2008, 32, 924–927.
  4. Makhlouf, H.R.; Ishak, K.G.; Goodman, Z.D. Epithelioid hemangioendothelioma of the liver: A clinicopathologic study of 137 cases. Cancer 1999, 85, 562–582.
  5. Mehrabi, A.; Kashfi, A.; Fonouni, H.; Schemmer, P.; Schmied, B.M.; Hallscheidt, P.; Schirmacher, P.; Weitz, J.; Friess, H.; Buchler, M.W.; et al. Primary malignant hepatic epithelioid hemangioendothelioma: A comprehensive review of the literature with emphasis on the surgical therapy. Cancer 2006, 107, 2108–2121.
  6. Alomari, A.I. The lollipop sign: A new cross-sectional sign of hepatic epithelioid hemangioendothelioma. Eur. J. Radiol. 2006, 59, 460–464.
  7. Liu, X.; Yu, H.; Zhang, Z.; Si, S.; Huang, J.; Tan, H.; Teng, F.; Yang, Z. MRI appearances of hepatic epithelioid hemangioendothelioma: A retrospective study of 57 patients. Insights Imaging 2022, 13, 65.
  8. Frota Lima, L.M.; Packard, A.T.; Broski, S.M. Epithelioid hemangioendothelioma: Evaluation by 18F-FDG PET/CT. Am. J. Nucl. Med. Mol. Imaging 2021, 11, 77–86.
  9. Dermawan, J.K.; Azzato, E.M.; Billings, S.D.; Fritchie, K.J.; Aubert, S.; Bahrami, A.; Barisella, M.; Baumhoer, D.; Blum, V.; Bode, B.; et al. YAP1-TFE3-fused hemangioendothelioma: A multi-institutional clinicopathologic study of 24 genetically-confirmed cases. Mod. Pathol. Off. J. United States Can. Acad. Pathol. Inc 2021, 34, 2211–2221.
  10. Bourgeau, M.; Martinez, A.; Deeb, K.K.; Reid, M.D.; Lewis, M.; Point du Jour, K.S.; Lai, J.; Shi, Q. Cytologic features of hepatic YAP1-TFE3 rearranged epithelioid hemangioendothelioma. Diagn. Cytopathol. 2021, 49, E447–E452.
  11. Flucke, U.; Vogels, R.J.; de Saint Aubain Somerhausen, N.; Creytens, D.H.; Riedl, R.G.; van Gorp, J.M.; Milne, A.N.; Huysentruyt, C.J.; Verdijk, M.A.; van Asseldonk, M.M.; et al. Epithelioid Hemangioendothelioma: Clinicopathologic, immunhistochemical, and molecular genetic analysis of 39 cases. Diagn. Pathol. 2014, 9, 131.
  12. Carter, C.S.; Patel, R.M. Cutaneous soft tissue tumors: Diagnostically disorienting epithelioid tumors that are not epithelial, and other perplexing mesenchymal lesions. Mod. Pathol. Off. J. United States Can. Acad. Pathol. Inc 2020, 33 (Suppl. 1), 66–82.
  13. Jo, V.Y.; Doyle, L.A. Refinements in Sarcoma Classification in the Current 2013 World Health Organization Classification of Tumours of Soft Tissue and Bone. Surg. Oncol. Clin. N. Am. 2016, 25, 621–643.
  14. Stacchiotti, S.; Miah, A.B.; Frezza, A.M.; Messiou, C.; Morosi, C.; Caraceni, A.; Antonescu, C.R.; Bajpai, J.; Baldini, E.; Bauer, S.; et al. Epithelioid hemangioendothelioma, an ultra-rare cancer: A consensus paper from the community of experts. ESMO Open 2021, 6, 100170.
  15. Szulzewsky, F.; Arora, S.; Hoellerbauer, P.; King, C.; Nathan, E.; Chan, M.; Cimino, P.J.; Ozawa, T.; Kawauchi, D.; Pajtler, K.W.; et al. Comparison of tumor-associated YAP1 fusions identifies a recurrent set of functions critical for oncogenesis. Genes Dev. 2020, 34, 1051–1064.
  16. Mohamed, A.D.; Tremblay, A.M.; Murray, G.I.; Wackerhage, H. The Hippo signal transduction pathway in soft tissue sarcomas. Biochim. Biophys. Acta 2015, 1856, 121–129.
  17. Anderson, W.J.; Fletcher, C.D.M.; Hornick, J.L. Loss of expression of YAP1 C-terminus as an ancillary marker for epithelioid hemangioendothelioma variant with YAP1-TFE3 fusion and other YAP1-related vascular neoplasms. Mod. Pathol. Off. J. United States Can. Acad. Pathol. Inc 2021, 34, 2036–2042.
  18. Hong, W.; Guan, K.L. The YAP and TAZ transcription co-activators: Key downstream effectors of the mammalian Hippo pathway. Semin. Cell Dev. Biol. 2012, 23, 785–793.
  19. Garcia, K.; Gingras, A.C.; Harvey, K.F.; Tanas, M.R. TAZ/YAP fusion proteins: Mechanistic insights and therapeutic opportunities. Trends Cancer 2022, 8, 1033–1045.
  20. Patel, N.R.; Salim, A.A.; Sayeed, H.; Sarabia, S.F.; Hollingsworth, F.; Warren, M.; Jakacky, J.; Tanas, M.; Oliveira, A.M.; Rubin, B.P.; et al. Molecular characterization of epithelioid haemangioendotheliomas identifies novel WWTR1-CAMTA1 fusion variants. Histopathology 2015, 67, 699–708.
  21. Driskill, J.H.; Zheng, Y.; Wu, B.K.; Wang, L.; Cai, J.; Rakheja, D.; Dellinger, M.; Pan, D. WWTR1(TAZ)-CAMTA1 reprograms endothelial cells to drive epithelioid hemangioendothelioma. Genes Dev. 2021, 35, 495–511.
  22. Martina, J.A.; Diab, H.I.; Li, H.; Puertollano, R. Novel roles for the MiTF/TFE family of transcription factors in organelle biogenesis, nutrient sensing, and energy homeostasis. Cell. Mol. Life Sci. CMLS 2014, 71, 2483–2497.
  23. Antonescu, C.R.; Le Loarer, F.; Mosquera, J.M.; Sboner, A.; Zhang, L.; Chen, C.L.; Chen, H.W.; Pathan, N.; Krausz, T.; Dickson, B.C.; et al. Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma. Genes Chromosomes Cancer 2013, 52, 775–784.
  24. Rosenbaum, E.; Jadeja, B.; Xu, B.; Zhang, L.; Agaram, N.P.; Travis, W.; Singer, S.; Tap, W.D.; Antonescu, C.R. Prognostic stratification of clinical and molecular epithelioid hemangioendothelioma subsets. Mod. Pathol. Off. J. United States Can. Acad. Pathol. Inc 2020, 33, 591–602.
  25. Seligson, N.D.; Awasthi, A.; Millis, S.Z.; Turpin, B.K.; Meyer, C.F.; Grand’Maison, A.; Liebner, D.A.; Hays, J.L.; Chen, J.L. Common Secondary Genomic Variants Associated with Advanced Epithelioid Hemangioendothelioma. JAMA Netw. Open 2019, 2, e1912416.
  26. Frezza, A.M.; Napolitano, A.; Miceli, R.; Badalamenti, G.; Brunello, A.; Buonomenna, C.; Casali, P.G.; Caraceni, A.; Grignani, G.; Gronchi, A.; et al. Clinical prognostic factors in advanced epithelioid haemangioendothelioma: A retrospective case series analysis within the Italian Rare Cancers Network. ESMO Open 2021, 6, 100083.
  27. Lytle, M.; Bali, S.D.; Galili, Y.; Bednov, B.; Murillo Alvarez, R.M.; Carlan, S.J.; Madruga, M. Epithelioid Hemangioendothelioma: A Rare Case of an Aggressive Vascular Malignancy. Am. J. Case Rep. 2019, 20, 864–867.
  28. Shibayama, T.; Makise, N.; Motoi, T.; Mori, T.; Hiraoka, N.; Yonemori, K.; Watanabe, S.I.; Esaki, M.; Morizane, C.; Okuma, T.; et al. Clinicopathologic Characterization of Epithelioid Hemangioendothelioma in a Series of 62 Cases: A Proposal of Risk Stratification and Identification of a Synaptophysin-positive Aggressive Subset. Am. J. Surg. Pathol. 2021, 45, 616–626.
  29. Li, Y.; Zhang, Z.; Zhang, C.; Li, J.; Zhang, B.; Dong, Y.; Cui, X. Establishment and Validation of a Nomogram Prognostic Model for Epithelioid Hemangioendothelioma. J. Oncol. 2022, 2022, 6254563.
  30. Tong, D.; Constantinidou, A.; Engelmann, B.; Chamberlain, F.; Thway, K.; Fisher, C.; Hayes, A.; Fotiadis, N.; Messiou, C.; Miah, A.B.; et al. The Role of Local Therapy in Multi-focal Epithelioid Haemangioendothelioma. Anticancer Res. 2019, 39, 4891–4896.
  31. Akizawa, T.; Nishizawa, T.; Yamada, S.; Ota, H.; Kida, G.; Tsukahara, Y.; Nakamura, T.; Oba, T.; Yamakawa, H.; Kawabe, R.; et al. Successful surgical treatment of epithelioid hemangioendothelioma involving multiple liver lesions and bilateral lung nodules. Respir. Med. Case Rep. 2022, 40, 101769.
  32. Kawka, M.; Mak, S.; Qiu, S.; Gall, T.M.H.; Jiao, L.R. Hepatic epithelioid hemangioendothelioma (HEHE)-rare vascular malignancy mimicking cholangiocarcinoma: A case report. Transl. Gastroenterol. Hepatol. 2022, 7, 42.
  33. Stacchiotti, S.; Frezza, A.M.; Blay, J.Y.; Baldini, E.H.; Bonvalot, S.; Bovee, J.; Callegaro, D.; Casali, P.G.; Chiang, R.C.; Demetri, G.D.; et al. Ultra-rare sarcomas: A consensus paper from the Connective Tissue Oncology Society community of experts on the incidence threshold and the list of entities. Cancer 2021, 127, 2934–2942.
  34. Frezza, A.M.; Ravi, V.; Lo Vullo, S.; Vincenzi, B.; Tolomeo, F.; Chen, T.W.; Teterycz, P.; Baldi, G.G.; Italiano, A.; Penel, N.; et al. Systemic therapies in advanced epithelioid haemangioendothelioma: A retrospective international case series from the World Sarcoma Network and a review of literature. Cancer Med. 2021, 10, 2645–2659.
  35. Agulnik, M.; Yarber, J.L.; Okuno, S.H.; von Mehren, M.; Jovanovic, B.D.; Brockstein, B.E.; Evens, A.M.; Benjamin, R.S. An open-label, multicenter, phase II study of bevacizumab for the treatment of angiosarcoma and epithelioid hemangioendotheliomas. Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 2013, 24, 257–263.
  36. Telli, T.A.; Okten, I.N.; Tuylu, T.B.; Demircan, N.C.; Arikan, R.; Alan, O.; Ercelep, O.; Ones, T.; Yildirim, A.T.; Dane, F.; et al. VEGF-VEGFR pathway seems to be the best target in hepatic epithelioid hemangioendothelioma: A case series with review of the literature. Curr. Probl. Cancer 2020, 44, 100568.
  37. Clinical Trial NCT04665206: Study to Evaluate VT3989 in Patients with Metastatic Solid Tumors Enriched for Tumors with NF2 Gene Mutations. Available online: https://www.australianclinicaltrials.gov.au/anzctr/trial/NCT04665206 (accessed on 7 August 2023).
  38. Clinical Trial NCT03148275: Trametinib in Treating Patients with Epithelioid Hemangioendothelioma That Is Metastatic, Locally Advanced, or Cannot Be Removed by Surgery. Available online: https:/classic.clinicaltrials.gov/ct2/show/NCT03148275 (accessed on 7 August 2023).
  39. Stacchiotti, S.; Simeone, N.; Lo Vullo, S.; Baldi, G.G.; Brunello, A.; Vincenzi, B.; Palassini, E.; Dagrada, G.; Collini, P.; Morosi, C.; et al. Activity of sirolimus in patients with progressive epithelioid hemangioendothelioma: A case-series analysis within the Italian Rare Cancer Network. Cancer 2021, 127, 569–576.
  40. Kollar, A.; Jones, R.L.; Stacchiotti, S.; Gelderblom, H.; Guida, M.; Grignani, G.; Steeghs, N.; Safwat, A.; Katz, D.; Duffaud, F.; et al. Pazopanib in advanced vascular sarcomas: An EORTC Soft Tissue and Bone Sarcoma Group (STBSG) retrospective analysis. Acta Oncol. 2017, 56, 88–92.
  41. Lau, A.; Malangone, S.; Green, M.; Badari, A.; Clarke, K.; Elquza, E. Combination capecitabine and bevacizumab in the treatment of metastatic hepatic epithelioid hemangioendothelioma. Ther. Adv. Med. Oncol. 2015, 7, 229–236.
  42. Chevreau, C.; Le Cesne, A.; Ray-Coquard, I.; Italiano, A.; Cioffi, A.; Isambert, N.; Robin, Y.M.; Fournier, C.; Clisant, S.; Chaigneau, L.; et al. Sorafenib in patients with progressive epithelioid hemangioendothelioma: A phase 2 study by the French Sarcoma Group (GSF/GETO). Cancer 2013, 119, 2639–2644.
  43. Pallotti, M.C.; Nannini, M.; Agostinelli, C.; Leoni, S.; Scioscio, V.D.; Mandrioli, A.; Lolli, C.; Saponara, M.; Pileri, S.; Bolondi, L.; et al. Long-term durable response to lenalidomide in a patient with hepatic epithelioid hemangioendothelioma. World J. Gastroenterol. 2014, 20, 7049–7054.
  44. Liu, X.; Zhou, R.; Si, S.; Liu, L.; Yang, S.; Han, D.; Tan, H. Case report: Successful treatment with the combined therapy of interferon-alpha 2b and anlotinib in a patient with advanced hepatic epithelioid hemangioendothelioma. Front. Med. 2022, 9, 1022017.
  45. Kounis, I.; Lewin, M.; Laurent-Bellue, A.; Poli, E.; Coilly, A.; Duclos-Vallee, J.C.; Guettier, C.; Adam, R.; Lerut, J.; Samuel, D.; et al. Advanced epithelioid hemangioendothelioma of the liver: Could lenvatinib offer a bridge treatment to liver transplantation? Ther. Adv. Med. Oncol. 2022, 14, 17588359221086909.
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Subjects: Biochemistry & Molecular Biology; Pathology; Oncology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Arwa Abdelmogod
,
Lia Papadopoulos
,
Stephen Riordan
,
Melvin Wong
,
Martin Weltman
,
Ratana Lim
,
Christopher McEvoy
,
Andrew Fellowes
,
Stephen Fox
,
Justin Bedő
,
Jocelyn Penington
,
Kym Pham
,
Oliver Hofmann
,
Joseph H. A. Vissers
,
Sean Grimmond
,
Gayanie Ratnayake
,
Michael Christie
,
Catherine Mitchell
,
William K. Murray
,
Kelly McClymont
,
Peter Luk
,
Anthony T. Papenfuss
,
Damien Kee
,
Clare L. Scott
,
David Goldstein
,
Holly E. Barker
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Update Date: 16 Oct 2023
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