Epithelioid hemangioendothelioma, an ultra-rare cancer: a consensus paper from the community of experts

S Stacchiotti¹, A B Miah², A M Frezza³, C Messiou⁴, C Morosi⁵, A Caraceni⁶, C R Antonescu⁷, J Bajpai⁸, E Baldini⁹, S Bauer¹⁰, R Biagini¹¹, S Bielack¹², J Y Blay¹³, S Bonvalot¹⁴, I Boukovinas¹⁵, J V M G Bovee¹⁶, K Boye¹⁷, T Brodowicz¹⁸, D Callegaro¹⁹, E De Alava²⁰, M Deoras-Sutliff²¹, A Dufresne¹³, M Eriksson²², C Errani²³, A Fedenko²⁴, V Ferraresi²⁵, A Ferrari²⁶, C D M Fletcher²⁷, X Garcia Del Muro²⁸, H Gelderblom²⁹, R A Gladdy³⁰, F Gouin³¹, G Grignani³², J Gutkovich³³, R Haas³⁴, N Hindi³⁵, P Hohenberger³⁶, P Huang³⁷, H Joensuu³⁸, R L Jones³⁹, C Jungels⁴⁰, B Kasper⁴¹, A Kawai⁴², A Le Cesne⁴³, F Le Grange⁴⁴, A Leithner⁴⁵, H Leonard⁴⁶, A Lopez Pousa⁴⁷, J Martin Broto⁴⁸, O Merimsky⁴⁹, P Merriam⁵⁰, R Miceli⁵¹, O Mir⁵², M Molinari⁵³, M Montemurro⁵⁴, G Oldani⁵⁵, E Palmerini⁵⁶, M A Pantaleo⁵⁷, S Patel⁵⁸, S Piperno-Neumann⁵⁹, C P Raut⁶⁰, V Ravi⁵⁸, A R A Razak⁶¹, P Reichardt⁶², B P Rubin⁶³, P Rutkowski⁶⁴, A A Safwat⁶⁵, C Sangalli⁶⁶, G Sapisochin⁶⁷, M Sbaraglia⁶⁸, S Scheipl⁶⁹, P Schöffski⁷⁰, D Strauss⁷¹, S J Strauss⁷², K Sundby Hall¹⁷, W D Tap⁷³, A Trama⁷⁴, A Tweddle⁷⁵, W T A van der Graaf⁷⁶, M A J Van De Sande⁷⁷, W Van Houdt⁷⁸, G van Oortmerssen⁷⁹, A J Wagner⁵⁰, M Wartenberg⁸⁰, J Wood⁸¹, N Zaffaroni⁸², C Zimmermann⁸³, P G Casali³, A P Dei Tos⁶⁸, A Gronchi¹⁹

Affiliations

¹ Adult Mesenchymal Tumor and Rare Cancer Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. Electronic address: silvia.stacchiotti@istitutotumori.mi.it.
² The Royal Marsden Hospital and The Institute of Cancer Research, London, UK.
³ Adult Mesenchymal Tumor and Rare Cancer Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
⁴ Department of Radiology, The Royal Marsden Hospital and The Institute of Cancer Research, London, UK.
⁵ Radiology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
⁶ Palliative Care Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
⁷ Department of Pathology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, USA.
⁸ Medical Oncology Department, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India.
⁹ Department of Radiation Oncology, Dana-Farber Cancer Center/Brigham and Women's Hospital, Boston, USA.
¹⁰ Department of Medical Oncology, West German Cancer Center, Sarcoma Center, University of Duisburg-Essen, University Hospital, Essen, Germany.
¹¹ Orthopaedic Department, Regina Elena National Cancer Institute, Rome, Italy.
¹² Klinikum Stuttgart - Olgahospital, Zentrum für Kinder-, Jugend- und Frauenmedizin, Stuttgart Cancer Center, Pädiatrische Onkologie, Hämatologie, Immunologie, Stuttgart, Germany.
¹³ Department of Medical Oncology, Centre Leon Berard, Université Claude Bernard Lyon, Unicancer, Lyon, France.
¹⁴ Department of Surgical Oncology, Institut Curie, Université Paris Sciences et Lettres, Paris, France.
¹⁵ Nordix, Athens, Greece.
¹⁶ Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
¹⁷ Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.
¹⁸ Medical University Vienna & General Hospital Department of Internal Medicine 1/Oncology, Vienna, Austria.
¹⁹ Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
²⁰ Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, Seville, Spain; Department of Normal and Pathological Cytology and Histology, School of Medicine, University of Seville, Seville, Spain.
²¹ The EHE Foundation, Wisconsin, USA.
²² Department of Oncology, Skane University Hospital and Lund University, Lund, Sweden.
²³ Orthopaedic Service, Musculoskeletal Oncology Department, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
²⁴ Medical Oncology Division, P.A. Herzen Cancer Research Institute, Moscow, Russian Federation.
²⁵ Sarcomas and Rare Tumors Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
²⁶ Paediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
²⁷ Department of Pathology Brigham & Women's Hospital, Boston, USA.
²⁸ University of Barcelona and Genitourinary Cancer and Sarcoma Unit Institut Català d'Oncologia, Hospitalet, Barcelona, Spain.
²⁹ Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
³⁰ University of Toronto and Lunenfeld-Tanenbaum Research Institute, Toronto, Canada.
³¹ Department of Surgery, Centre Leon Berard, Lyon, France.
³² Division of Medical Oncology, Candiolo Cancer Institute, FPO - IRCCS, Candiolo, Italy.
³³ The EHE Foundation, Wisconsin, USA; NUY Langone Medical Center, New York, USA.
³⁴ Department of Radiotherapy, the Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Radiotherapy, the Leiden University Medical Center, Leiden, the Netherlands.
³⁵ Group of Advanced Therapies and Biomarkers in Sarcoma, Institute of Biomedicine of Seville (IBIS, HUVR, CSIC, Universidad de Sevilla), Seville, Spain.
³⁶ Division of Surgical Oncology & Thoracic Surgery, Mannheim University Medical Center, University of Heidelberg, Heidelberg, Germany.
³⁷ Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
³⁸ Department of Oncology, Helsinki University Hospital & Helsinki University, Helsinki, Finland.
³⁹ Department of Cancer, The Royal Marsden Hospital and The Institute of Cancer Research, London, UK.
⁴⁰ Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
⁴¹ University of Heidelberg, Mannheim University Medical Center, Sarcoma Unit, Mannheim, Germany.
⁴² Musculoskeletal Oncology and Rehabilitation Medicine, Rare Cancer Center National Cancer Center Hospital, Tokyo, Japan.
⁴³ International Department, Gustave Roussy, Villejuif, France.
⁴⁴ UCLH - University College London Hospitals NHS Foundation Trust, London, UK.
⁴⁵ Department of Orthopaedics and Trauma Medical University Graz, Graz, Austria.
⁴⁶ Chair of Trustees of the EHE Rare Cancer Charity (UK), Charity number 1162472.
⁴⁷ Medical Oncology Department, Hospital Universitario Santa Creu i Sant Pau, Barcelona, Spain.
⁴⁸ Hospital Universitario Fundación Jimenez Diaz, Madrid, Spain.
⁴⁹ Unit of Soft Tissue and Bone Oncology, Division of Oncology, Tel-Aviv Medical Center affiliated with Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
⁵⁰ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA.
⁵¹ Department of Clinical Epidemiology and Trial Organisation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
⁵² Sarcoma Group, Gustave Roussy, Villejuif, France.
⁵³ University of Pittsburgh Medical Center, Thomas Starzl Transplant Institute, Pittsburgh, USA.
⁵⁴ Oncology, CHUV Lausanne, Lausanne, Switzerland.
⁵⁵ Division of Abdominal Surgery, University Hospitals of Geneva, Geneva, Switzerland.
⁵⁶ Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
⁵⁷ Division of Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
⁵⁸ Sarcoma Center, The University of Texas M.D. Anderson Cancer Center, Houston, USA.
⁵⁹ Department of Medical Oncology, Institut Curie, Paris, France.
⁶⁰ Department of Surgery, Brigham and Women's Hospital, Boston, USA; Center for Sarcoma and Bone Oncology, Harvard Medical School, Boston, USA; Dana Farber Cancer Center, Harvard Medical School, Boston, USA.
⁶¹ Princess Margaret Cancer Centre and Sinai Healthcare System & Faculty of Medicine, University of Toronto, Toronto, Canada.
⁶² Helios Klinikum Berlin-Buch, Department of Oncology and Palliative Care, Berlin, Germany.
⁶³ Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, USA.
⁶⁴ Maria Sklodowska-Curie National Research Institute of Oncology, Department of Soft Tissue/Bone Sarcoma and Melanoma, Warsaw, Poland.
⁶⁵ Aarhus University Hospital, Aarhus, Denmark.
⁶⁶ Department of Radiation Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
⁶⁷ Multi-Organ Transplant and HPB Surgical Oncology, Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Canada.
⁶⁸ Department of Pathology, Azienda Ospedaliera Università Padova, Padua, Italy.
⁶⁹ Department of Orthopaedics and Trauma, Medical University of Graz, Graz, Austria.
⁷⁰ Leuven Cancer Institute, Leuven, Belgium.
⁷¹ Department of Surgery, The Royal Marsden Hospital and The Institute of Cancer Research, London, UK.
⁷² University College London Hospital, London, UK.
⁷³ Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, USA.
⁷⁴ Department of Research, Evaluative Epidemiology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
⁷⁵ Palliative Care, The Royal Marsden Hospital and The Institute of Cancer Research London.
⁷⁶ Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
⁷⁷ Department of Orthopedic Surgery Bone and Soft Tissue Tumor Unit, Leiden University Medical Center, Leiden, The Netherlands.
⁷⁸ Sarcoma and Melanoma Unit, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
⁷⁹ Co-Chair of Sarcoma Patients EuroNet (SPAEN), Woelfersheim, Germany & Chairman of the Dutch organisation for sarcoma patients (Patiëntenplatform Sarcomen), Guest researcher at Leiden University (Leiden Institute for Advanced Computer Science), Leiden University, Leiden, The Netherlands.
⁸⁰ Chair of the Board of Directors of Sarcoma Patients EuroNet (SPAEN), Sarcoma Patients EuroNet (SPAEN), Woelfersheim, Germany.
⁸¹ The Royal Marsden NHS Foundation Trust, London, UK.
⁸² Molecular Pharmacology Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
⁸³ Department of Supportive Care, Princess Margaret Cancer Centre and Division of Palliative Medicine, Department of Medicine, University of Toronto, Toronto, Canada.

PMID: 34090171
PMCID: PMC8182432
DOI: 10.1016/j.esmoop.2021.100170

Review

Epithelioid hemangioendothelioma, an ultra-rare cancer: a consensus paper from the community of experts

S Stacchiotti et al. ESMO Open. 2021 Jun.

. 2021 Jun;6(3):100170.

doi: 10.1016/j.esmoop.2021.100170. Epub 2021 Jun 2.

Authors

Affiliations

¹ Adult Mesenchymal Tumor and Rare Cancer Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. Electronic address: silvia.stacchiotti@istitutotumori.mi.it.
² The Royal Marsden Hospital and The Institute of Cancer Research, London, UK.
³ Adult Mesenchymal Tumor and Rare Cancer Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
⁴ Department of Radiology, The Royal Marsden Hospital and The Institute of Cancer Research, London, UK.
⁵ Radiology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
⁶ Palliative Care Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
⁷ Department of Pathology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, USA.
⁸ Medical Oncology Department, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India.
⁹ Department of Radiation Oncology, Dana-Farber Cancer Center/Brigham and Women's Hospital, Boston, USA.
¹⁰ Department of Medical Oncology, West German Cancer Center, Sarcoma Center, University of Duisburg-Essen, University Hospital, Essen, Germany.
¹¹ Orthopaedic Department, Regina Elena National Cancer Institute, Rome, Italy.
¹² Klinikum Stuttgart - Olgahospital, Zentrum für Kinder-, Jugend- und Frauenmedizin, Stuttgart Cancer Center, Pädiatrische Onkologie, Hämatologie, Immunologie, Stuttgart, Germany.
¹³ Department of Medical Oncology, Centre Leon Berard, Université Claude Bernard Lyon, Unicancer, Lyon, France.
¹⁴ Department of Surgical Oncology, Institut Curie, Université Paris Sciences et Lettres, Paris, France.
¹⁵ Nordix, Athens, Greece.
¹⁶ Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
¹⁷ Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.
¹⁸ Medical University Vienna & General Hospital Department of Internal Medicine 1/Oncology, Vienna, Austria.
¹⁹ Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
²⁰ Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, Seville, Spain; Department of Normal and Pathological Cytology and Histology, School of Medicine, University of Seville, Seville, Spain.
²¹ The EHE Foundation, Wisconsin, USA.
²² Department of Oncology, Skane University Hospital and Lund University, Lund, Sweden.
²³ Orthopaedic Service, Musculoskeletal Oncology Department, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
²⁴ Medical Oncology Division, P.A. Herzen Cancer Research Institute, Moscow, Russian Federation.
²⁵ Sarcomas and Rare Tumors Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
²⁶ Paediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
²⁷ Department of Pathology Brigham & Women's Hospital, Boston, USA.
²⁸ University of Barcelona and Genitourinary Cancer and Sarcoma Unit Institut Català d'Oncologia, Hospitalet, Barcelona, Spain.
²⁹ Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
³⁰ University of Toronto and Lunenfeld-Tanenbaum Research Institute, Toronto, Canada.
³¹ Department of Surgery, Centre Leon Berard, Lyon, France.
³² Division of Medical Oncology, Candiolo Cancer Institute, FPO - IRCCS, Candiolo, Italy.
³³ The EHE Foundation, Wisconsin, USA; NUY Langone Medical Center, New York, USA.
³⁴ Department of Radiotherapy, the Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Radiotherapy, the Leiden University Medical Center, Leiden, the Netherlands.
³⁵ Group of Advanced Therapies and Biomarkers in Sarcoma, Institute of Biomedicine of Seville (IBIS, HUVR, CSIC, Universidad de Sevilla), Seville, Spain.
³⁶ Division of Surgical Oncology & Thoracic Surgery, Mannheim University Medical Center, University of Heidelberg, Heidelberg, Germany.
³⁷ Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
³⁸ Department of Oncology, Helsinki University Hospital & Helsinki University, Helsinki, Finland.
³⁹ Department of Cancer, The Royal Marsden Hospital and The Institute of Cancer Research, London, UK.
⁴⁰ Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
⁴¹ University of Heidelberg, Mannheim University Medical Center, Sarcoma Unit, Mannheim, Germany.
⁴² Musculoskeletal Oncology and Rehabilitation Medicine, Rare Cancer Center National Cancer Center Hospital, Tokyo, Japan.
⁴³ International Department, Gustave Roussy, Villejuif, France.
⁴⁴ UCLH - University College London Hospitals NHS Foundation Trust, London, UK.
⁴⁵ Department of Orthopaedics and Trauma Medical University Graz, Graz, Austria.
⁴⁶ Chair of Trustees of the EHE Rare Cancer Charity (UK), Charity number 1162472.
⁴⁷ Medical Oncology Department, Hospital Universitario Santa Creu i Sant Pau, Barcelona, Spain.
⁴⁸ Hospital Universitario Fundación Jimenez Diaz, Madrid, Spain.
⁴⁹ Unit of Soft Tissue and Bone Oncology, Division of Oncology, Tel-Aviv Medical Center affiliated with Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
⁵⁰ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA.
⁵¹ Department of Clinical Epidemiology and Trial Organisation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
⁵² Sarcoma Group, Gustave Roussy, Villejuif, France.
⁵³ University of Pittsburgh Medical Center, Thomas Starzl Transplant Institute, Pittsburgh, USA.
⁵⁴ Oncology, CHUV Lausanne, Lausanne, Switzerland.
⁵⁵ Division of Abdominal Surgery, University Hospitals of Geneva, Geneva, Switzerland.
⁵⁶ Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
⁵⁷ Division of Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
⁵⁸ Sarcoma Center, The University of Texas M.D. Anderson Cancer Center, Houston, USA.
⁵⁹ Department of Medical Oncology, Institut Curie, Paris, France.
⁶⁰ Department of Surgery, Brigham and Women's Hospital, Boston, USA; Center for Sarcoma and Bone Oncology, Harvard Medical School, Boston, USA; Dana Farber Cancer Center, Harvard Medical School, Boston, USA.
⁶¹ Princess Margaret Cancer Centre and Sinai Healthcare System & Faculty of Medicine, University of Toronto, Toronto, Canada.
⁶² Helios Klinikum Berlin-Buch, Department of Oncology and Palliative Care, Berlin, Germany.
⁶³ Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, USA.
⁶⁴ Maria Sklodowska-Curie National Research Institute of Oncology, Department of Soft Tissue/Bone Sarcoma and Melanoma, Warsaw, Poland.
⁶⁵ Aarhus University Hospital, Aarhus, Denmark.
⁶⁶ Department of Radiation Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
⁶⁷ Multi-Organ Transplant and HPB Surgical Oncology, Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Canada.
⁶⁸ Department of Pathology, Azienda Ospedaliera Università Padova, Padua, Italy.
⁶⁹ Department of Orthopaedics and Trauma, Medical University of Graz, Graz, Austria.
⁷⁰ Leuven Cancer Institute, Leuven, Belgium.
⁷¹ Department of Surgery, The Royal Marsden Hospital and The Institute of Cancer Research, London, UK.
⁷² University College London Hospital, London, UK.
⁷³ Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, USA.
⁷⁴ Department of Research, Evaluative Epidemiology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
⁷⁵ Palliative Care, The Royal Marsden Hospital and The Institute of Cancer Research London.
⁷⁶ Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
⁷⁷ Department of Orthopedic Surgery Bone and Soft Tissue Tumor Unit, Leiden University Medical Center, Leiden, The Netherlands.
⁷⁸ Sarcoma and Melanoma Unit, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
⁷⁹ Co-Chair of Sarcoma Patients EuroNet (SPAEN), Woelfersheim, Germany & Chairman of the Dutch organisation for sarcoma patients (Patiëntenplatform Sarcomen), Guest researcher at Leiden University (Leiden Institute for Advanced Computer Science), Leiden University, Leiden, The Netherlands.
⁸⁰ Chair of the Board of Directors of Sarcoma Patients EuroNet (SPAEN), Sarcoma Patients EuroNet (SPAEN), Woelfersheim, Germany.
⁸¹ The Royal Marsden NHS Foundation Trust, London, UK.
⁸² Molecular Pharmacology Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
⁸³ Department of Supportive Care, Princess Margaret Cancer Centre and Division of Palliative Medicine, Department of Medicine, University of Toronto, Toronto, Canada.

PMID: 34090171
PMCID: PMC8182432
DOI: 10.1016/j.esmoop.2021.100170

Abstract

Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.

Keywords: diagnosis; epithelioid hemangioendothelioma; guidelines; management; sarcoma; treatment.

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Conflict of interest statement

Disclosure SS: Honoraria, consultancy or advisory role: Adaptimmune, Bayer, Daiichi Sankyo, Deciphera, Epizyme, Eli Lilly, Glaxo, Immune Design, Karyopharm, MaxiVAX, Novartis, PharmaMar; Institutional financial interests: Advenchen, Amgen Dompè, Bayer, Epizyme, Eli Lilly, Daiichi Sankyo, Glaxo, Hutchison MediPharma, Karyopharm, Novartis, Pfizer, PharmaMar, SpringWorks. AMF: Institutional financial interests: Advenchen, Amgen Dompè, Bayer, Epizyme, Eli Lilly, Daiichi Sankyo, Glaxo, Hutchison MediPharma, Karyopharm, Novartis, Pfizer, PharmaMar, SpringWorks. AC: Advisory board: Angelini Holding S.p.A, Shionogi B.V., L. Molteni & C., Kyowa Kirin S.r.l.; invited speaker King Faisal Specialist Hospital & Research Center. JB: Uncompensated advisory board: Novartis; research funding (institutional) from Eli Lilly, Novartis, Roche, Samsung Bioepis Co. Ltd, Paxman Coolers Ltd, Sun Pharma. SB: Personal fees from Bayer, Deciphera, Lilly, Daiichi Sankyo, Plexxikon, Exelixis, PharmaMar, Lilly, Roche, GlaxoSmithKline (GSK); grants from Incyte, grants and personal fees from Blueprint Medicines, Novartis; research funding (institutional) Pfizer. SB: Research support from Novartis, Incyte, Blueprint Medicines; honoraria or consultation fees from Novartis, Lilly, Pfizer, PharmaMar, Bayer. JYB: Research support and honoraria from Bristol-Myers Squibb (BMS), Merck Sharp & Dohme (MSD), Roche, Bayer, Novartis, GSK, Deciphera, OSE Pharma, AstraZeneca. Member of the supervisory board: Innate Pharma. SB: Honoraria from PharmaMar. JVMGB: Research funding from TRACON Pharmaceuticals; Royalties from UptoDate and Wolters Kluwer. KB: Advisory: Bayer; expert testimony: Bayer; invited speaker: Lilly; institutional research funding: Lilly. TB: Advisory board from Bayer; honoraria: Novartis, PharmaMar, Eli Lilly. ME: Consultant for Blueprint Medicines; advisory boards for Clinigen and Bayer. AF; Honoraria: Amgen, Lilly, Roche, MSD; research funding; MSD, Roche, Clovis, AstraZeneca. BMS; Abbvie. VF: Consulting or advisory role: BMS, MSD, Novartis; speakers' bureau: BMS, MSD, Novartis, Pierre Fabre. XGdM: Advisory boards for Ipsen, EUSA Pharma, BMS, Pfizer, Roche, PharmaMar; honoraria from Lilly, Astellas Pharma, Eisai, Pfizer. HG: Reports institutional funding from Novartis, Deciphera. FG: Honoraria from Deciphera, Amgen; stock ownership from Atlanthera; royalties from Zimmer. GG: Grants/research supports: PharmaMar, Novartis, Bayer; honoraria or consultation fees: PharmaMar, Bayer, Merck, Eisai, Novartis, Glaxo. NH: Research grants from PharmaMar, Eisai, Immix BioPharma and Novartis; honoraria and travel grants from PharmaMar; and research funding for clinical studies (institutional) from PharmaMar, Eli Lilly and Company, Adaptimmune Therapeutics, AROG, Bayer, Eisai, Lixte, Karyopharm, Deciphera, GSK, Novartis, Blueprint, Nektar, Forma, Amgen and Daiichi Sankyo. PH: Honoraria for consultations and speaker's fees from Roche, GSK, AstraZeneca, Pfizer, PharmaMar, Lilly, Nanobiotix, Novartis, EISAI, Nektar, Sirtex and Pekkip Oncology; research funding and educational grants from Novartis, Siemens, Boehringer, Merck, BLUMedicine and Springer; trial support to my institution by Novartis and Siemens. PH: Advisory roles for Sarcoma UK and National Leiomyosarcoma Foundation; research grants from Sarcoma UK, Desmoid Tumor Research Foundation, Children's Cancer and Leukemia Group and Cancer Research UK, funding from EHE Rare Cancer Charity (UK). HJ: Chair of the Orion Pharma Scientific Advisory Board, chair of Neutron Therapeutics Advisory Board; he has been employed by Orion Pharma, and owns stocks of Orion Pharma and Sartar Therapeutics. RJ: Advisory board Adaptimmune, Athenex, Bayer, Boehringer Ingelheim, Blueprint, Clinigen, Eisai, Epizyme, Daichii, Deciphera, Immune Design, Lilly, Merck, PharmaMar, SpringWorks, TRACON, UptoDate; honoraria: BMS, MSD, Novartis, Pierre Fabre, Merck, Sanofi. CJ: Travel grants from PharmaMar, Ipsen. BK: Reports advisory board Bayer, Blueprint, Boehringer Ingelheim, GSK, PharmaMar, SpringWorks; research funding (institutional) PharmaMar, SpringWorks. AK: Advisory board Otsuka; invited speaker for Daiichi Sankyo, Eisai, Eli Lilly, Novartis, Taiho. ALC: Advisory boards with Lilly, PharmaMar, Deciphera, Blueprint. AL: Reports institutional financial interest, and educational grant from Alphamed, ImplanTec, Johnson & Johnson, Medacta. JMB: Research grants from PharmaMar, Eisai, Immix BioPharma and Novartis; honoraria from PharmaMar, Lilly, Bayer, Eisai, Daichii. Travel grants from PharmaMar; advisory board: Roche, Lilly, PharmaMar; research funding for clinical studies (institutional) from PharmaMar, Eli Lilly and Company, Adaptimmune Therapeutics, AROG, Bayer, Eisai, Lixte, Karyopharm, Deciphera, GSK, Novartis, Blueprint, Nektar, Forma, Amgen, Celgene, Pfizer, BMS, and Daiichi Sankyo. OMe: Consultation fees from MSD, AstraZeneca, Takeda, Megapharm, Medison, Progenetics; supported lecture: MSD, AstraZeneca, Roche, BMS. OMi: Consultancy for Amgen, AstraZeneca, Bayer, BMS, Eli Lilly, Ipsen, Lundbeck, MSD, Novartis, Pfizer, Roche, Servier, Vifor Pharma; Speakers bureau: Eli Lilly, Roche, Servier; Stock ownership: Amplitude Surgical, Ipsen, Transgene. EP: Advisory boards for Amgen, Daiichi Sankyo, Lilly, Deciphera, EUSA Pharma, and SynOx Therapeutics; research support from BMS, Pfizer, PharmaMar, Daiichi Sankyo, Incyte; travel support from Lilly, PharmaMar and Takeda. MAP: Advisory board Lilly, Pfizer, Roche. SP: Consultant: Deciphera, Daichi Sankyo, Dova, Epizyme, MaxiVAX; Research/Grant Support: Blueprint Medicines, Hutchison MediPharma. SPN: Advisory board for Immunocore. AR: Consulting role with Lilly, Merck, Boehringer Ingelheim; research funding from CASI Pharmaceuticals, Boehringer Ingelheim, Lilly, Novartis, Deciphera, Karyopharm Therapeutics, Pfizer, Roche/Genentech, Boston Biomedical, BMS, MedImmune, Amgen, GSK, Blueprint Medicines, Merck, AbbVie, Adaptimmune. PRe: Advisory roles for Bayer, Clinigen, Roche, MSD, Deciphera, PharmaMar, Mundibiopharma, and speaker's honoraria from Lilly, PharmaMar. BPR: Reports advisory board from Deciphera. PRu: Advisory board MSD, BMS, Merck, Sanofi, Pierre Fabre, Blueprint Medicines; honoraria from BMS, MSD, Novartis, Pierre Fabre, Merck, Sanofi. MS: Travel grant from PharmaMar. SJS: Advisory boards for Lilly and GSK. WDT: Reports fees from Eli Lilly, EMD Serono, Eisai, Mundipharma, C4 Therapeutics, Daiichi Sankyo, Blueprint, GSK, Agios Pharmaceuticals, NanoCarrier, Deciphera; patent Companion Diagnostic for CDK4 inhibitors - 14/854 329 pending to MSKCC/SKI, and patent Enigma and CDH18 as companion Diagnostics for CDK4 inhibition – SKI2016-021-03 pending to MSKCC/SKI and Scientific Advisory Board - Certis Oncology Solutions, Stock Ownership Üo-Founder - Atropos Therapeutics; Stock Ownership/scientific advisory board Innova Therapeutics. WTAWDG: Reports consultancy from SpringWorks to her institute; research grant support from Novartis and Lilly to her institute; advisory for Bayer to her institute. AJW: Consulting: Daiichi Sankyo, Deciphera, Epizyme, Mundipharma; research support to my Institution: Aadi Bioscience, Daiichi Sankyo, Deciphera, Eli Lilly, Karyopharm, Plexxikon. PGC: Honoraria, consultancy or advisory role: Bayer, Deciphera, Eisai, Eli Lilly, Pfizer. Institutional financial interest: Advenchen Laboratories, Amgen Dompé, AROG Pharmaceuticals, Bayer, Blueprint Medicines, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme, Glaxo, Hutchinson MediPharma, Karyopharm, Novartis, Pfizer, PharmaMar. APDT: Honoraria: Roche, Bayer, Pharmamar, MSD. AG: Compensations for Advisory boards from Novartis, Pfizer, Bayer, Lilly, PharmaMar, SpringWorks, Nanobiotix; honoraria from Lilly and PharmaMar; institutional research grants from PharmaMar. All other authors have declared no conflicts of interest.

Figures

**Figure 1**
Pathologic features of epithelioid hemangioendothelioma (EHE). (Panel A) Hematoxylin–eosin staining in CAMTA1-rearranged EHE: epithelioid cells organized in strands and cords set in a collagenous stroma are typically observed. The neoplastic cells contain intracytoplasmic vacuoles. (Panel B) CAMTA1 immunostaining shows CAMTA1 nuclear expression in tumor cells. (Panel C) Hematoxylin–eosin staining in TFE3-rearranged EHE: tumor cells tend to show larger eosinophilic cytoplasm. (Panel D) TFE3 immunostaining shows the nuclear expression of TFE3. CAMTA1, calmodulin binding transcription activator 1; TFE3, transcription factor E3.

**Figure 2**
Primary, soft tissue epithelioid hemangioendothelioma (EHE). Contrast-enhanced T1-weighted magnetic resonance imaging (MRI), axial view (A) and contrast-enhanced T1- Spectroscopie Dans le Proche Infrarouge (SPIR)-weighted MRI coronal view (B), showing a classic EHE with an infiltrative growth pattern in the vastus medialis (red circle). Surgical specimen cut along the longitudinal axis showing the macroscopic appearance of the tumor (black circle, C). Contrast-enhanced T1-SPIR-weighted MRI, axial view (D) and coronal view (E), showing a more aggressive EHE with infiltrative growth pattern and necrosis in the anterior aspect of the proximal forearm. Surgical specimen cut along the longitudinal axis showing the macroscopic appearance of the tumor (F). Contrast-enhanced T1-weighted MRI, axial view (G) and coronal view (H) showing a classic EHE with a nodular growth pattern in the medial aspect of the arm arising from the brachial vessels. Surgical specimen cut along the axial axis, showing the macroscopic appearance of the tumor (I, brachial artery is cannulated by the wire).

**Figure 3**
Thoracic epithelioid hemangioendothelioma (EHE). (A) Computed tomography (CT) scan of the chest, lung window, axial view, showing solid pulmonary nodules in both lungs (red arrows). (B) CT scan of the chest, lung window, axial view, showing multifocal areas of reticulonodular pattern in both lungs (red arrows). (C) Contrast enhanced CT scan of the chest, venous phase, soft tissue window, axial view, showing diffuse pleural involvement (red arrow) with mediastinal shift. (D) CT scan of the chest, lung window, axial view, showing pleural thickening (yellow arrow) and parenchymal lesions (red arrows).

**Figure 4**
Hepatic epithelioid hemangioendothelioma (EHE). (A) T2-weighted magnetic resonance imaging of the abdomen, axial view, showing hepatic lesions with a target sign (red arrow). (B) Contrast enhanced computed tomography (CT) scan of the abdomen, portal phase, axial view, showing multiple peripheral low attenuation hepatic lesions. (C) Contrast enhanced CT scan of the abdomen, portal phase, axial view, showing multiple peripheral low attenuation hepatic lesions and capsular retraction (red arrow).

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References

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Epithelioid hemangioendothelioma, an ultra-rare cancer: a consensus paper from the community of experts

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