Advertisement

Epithelioid Hemangioendothelioma: Update on Diagnosis and Treatment

  • Ari Rosenberg
  • Mark Agulnik
Sarcoma (SH Okuno, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Sarcoma

Opinion statement

Epithelioid hemangioendothelioma (EHE) is an extremely rare sarcoma, as such it can pose a clinical dilemma based solely on its rarity. Also, the spectrum of disease varies greatly between an indolent disease and aggressive disease with widespread metastases. In our clinical practice, the primary focus has been to get a handle on the aggressive nature of the disease, which will then dictate how urgently one needs to treat the patient. Pathological review with immunohistochemistry and molecular characterization is paramount. Our treatment strategy is watch-and-wait versus active therapy on clinical trial or based on results of prior clinical trials. There is evidence to support the use of chemotherapeutics and targeted therapies specifically focusing on anti-angiogenesis. The current landscape of oncology with the emergence and excitement of immunotherapy could also translate in a role for immunotherapy in this disease. While rare, there is certainly no reason that research and trials for patients with EHE should not remain on utmost importance for those of us who specialize in the treatment of sarcomas.

Keywords

Epithelioid hemangioendothelioma Sarcoma WWTR1 CAMTA1 

Notes

Compliance with Ethical Standards

Conflict of Interest

Ari Rosenberg and Mark Agulnik declare they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance, •• Of major importance

  1. 1.
    Sardaro A, Bardoscia L, Petruzzelli MF, Portaluri M. Epithelioid hemangioendothelioma: an overview and update on a rare vascular tumor. Oncol Rev. 2014;8(2):259.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Weiss SW, Enzinger FM. Epithelioid hemangioendothelioma: a vascular tumor often mistaken for a carcinoma. Cancer. 1982;50(5):970–81.PubMedCrossRefGoogle Scholar
  3. 3.
    Tanas MR, Sboner A, Oliveira AM, Erickson-Johnson MR, Hespelt J, Hanwright PJ, et al. Identification of a disease-defining gene fusion in epithelioid hemangioendothelioma. Sci Transl Med. 2011;3(98):98ra82.PubMedCrossRefGoogle Scholar
  4. 4.
    Doyle LA. Sarcoma classification: an update based on the 2013 World Health Organization classification of tumors of soft tissue and bone. Cancer. 2014;120(12):1763–74.PubMedCrossRefGoogle Scholar
  5. 5.
    Amin RMS, Hiroshima K, Kokubo T, Nishikawa M, Narita M, Kuroki M, et al. Risk factors and independent predictors of survival in patients with pulmonary epithelioid haemangioendothelioma. Review of the literature and a case report. Respirology. 2006;11(6):818–25.PubMedCrossRefGoogle Scholar
  6. 6.
    Lau K, Massad M, Pollak C, Rubin C, Yeh J, Wang J, et al. Clinical patterns and outcome in epithelioid hemangioendothelioma with or without pulmonary involvement: insights from an internet registry in the study of a rare cancer. Chest. 2011;140(5):1312–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Kitaichi M, Nagai S, Nishimura K, Itoh H, Asamoto H, Izumi T, et al. Pulmonary epithelioid haemangioendothelioma in 21 patients, including three with partial spontaneous regression. Eur Respir J. 1998;12(1):89–96.PubMedCrossRefGoogle Scholar
  8. 8.
    Bagan P, Hassan M, Le Pimpec BF, Peyrard S, Souilamas R, Danel C, et al. Prognostic factors and surgical indications of pulmonary epithelioid hemangioendothelioma: a review of the literature. Ann Thorac Surg. 2006;82(6):2010–3.PubMedCrossRefGoogle Scholar
  9. 9.
    Gómez-Arellano LI, Ferrari-Carballo T, Domínguez-Malagón HR. Multicentric epithelioid hemangioendothelioma of bone. Report of a case with radiologic-pathologic correlation. Ann Diagn Pathol. 2012;16(1):43–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Larochelle O, Perigny M, Lagace R, Dion N, Giguere C. Best cases from the AFIP: epithelioid hemangioendothelioma of bone. Radiographics : a review publication of the Radiological Society of North America, Inc. 2006;26(1):265–70.CrossRefGoogle Scholar
  11. 11.
    Albakr A, Schell M, Drew B, Cenic A. Epithelioid hemangioendothelioma of the spine: Case report and review of the literature. J Spine Surg. 2017;3(2):250–9.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Ma J, Wang L, Mo W, Yang X, Xiao J. Epithelioid hemangioendotheliomas of the spine: clinical characters with middle and long-term follow-up under surgical treatments. Eur Spine J. 2011;20(8):1371–6.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Woo JH, Kim TJ, Lee KS, Kim TS, Kim BT. Epithelioid hemangioendothelioma in the thorax: clinicopathologic, CT, PET, and prognostic features. Medicine (Baltimore). 2016;95(30):e4348.CrossRefGoogle Scholar
  14. 14.
    Gan LU, Chang R, Jin H, Yang LI. Typical CT and MRI signs of hepatic epithelioid hemangioendothelioma. Oncol Lett. 2016;11(3):1699–706.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Errani C, Zhang L, Panicek DM, Healey JH, Antonescu CR. Epithelioid hemangioma of bone and soft tissue: a reappraisal of a controversial entity. Clin Orthop Relat Res. 2012;470(5):1498–506.PubMedCrossRefGoogle Scholar
  16. 16.
    Rosengarten D, Kramer MR, Amir G, Fuks L, Berkman N. Pulmonary epithelioid hemangioendothelioma. Isr Med Assoc J: IMAJ. 2011;13(11):676–9.PubMedGoogle Scholar
  17. 17.
    Deyrup AT, Tighiouart M, Montag AG, Weiss SW. Epithelioid hemangioendothelioma of soft tissue: a proposal for risk stratification based on 49 cases. Am J Surg Pathol. 2008;32(6):924–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Flucke U, Vogels RJ, de Saint Aubain Somerhausen N, Creytens DH, Riedl RG, van Gorp JM, et al. Epithelioid hemangioendothelioma: clinicopathologic, immunhistochemical, and molecular genetic analysis of 39 cases. Diagnostic Pathology. 2014;9(1):131.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    •• Anderson T, Zhang L, Hameed M, Rusch V, Travis WD, Antonescu CR. Thoracic epithelioid malignant vascular tumors: a clinicopathologic study of 52 cases with emphasis on pathologic grading and molecular studies of WWTR1-CAMTA1 fusions. Am J Surg Pathol. 2015;39(1):132–9. This large series which included 52 patients help us better understand the pathology and molecular profile of these rare tumorsPubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Murali R, Zarka MA, Ocal IT, Tazelaar HD. Cytologic features of epithelioid hemangioendothelioma. Am J Clin Pathol. 2011;136(5):739–46.PubMedCrossRefGoogle Scholar
  21. 21.
    Gill R, O'Donnell RJ, Horvai A. Utility of immunohistochemistry for endothelial markers in distinguishing epithelioid hemangioendothelioma from carcinoma metastatic to bone. Arch Pathol Lab Med. 2009;133(6):967–72.PubMedGoogle Scholar
  22. 22.
    Errani C, Zhang L, Shao SY, Hajdu M, Singer S, Maki RG, et al. A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites. Genes Chromosom Cancer. 2011;50(8):644–53.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Tanas MR, Ma S, Jadaan FO, Ng CKY, Weigelt B, Reis-Filho JS, et al. Mechanism of action of a WWTR1(TAZ)-CAMTA1 fusion oncoprotein. Oncogene. 2015;35:929.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Thway K, Mentzel T, Perrett CM, Calonje E. Multicentric visceral epithelioid hemangioendothelioma, with extremity dermal deposits, unusual late recurrence on the nasal bridge and TFE3 gene rearrangement. Hum Pathol 2017.Google Scholar
  25. 25.
    Doyle LA, Fletcher CD, Hornick JL. Nuclear expression of CAMTA1 distinguishes epithelioid hemangioendothelioma from histologic mimics. Am J Surg Pathol. 2016;40(1):94–102.PubMedCrossRefGoogle Scholar
  26. 26.
    Antonescu CR, Le Loarer F, Mosquera J-M, Sboner A, Zhang L, Chen C-L, et al. Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma. Genes Chromosom Cancer. 2013;52(8):775–84.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Lee SJ, Yang WI, Chung WS, Kim SK. Epithelioid hemangioendotheliomas with TFE3 gene translocations are compossible with CAMTA1 gene rearrangements. Oncotarget. 2016;7(7):7480–8.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Kanemura S, Kuribayashi K, Moriya Y, Shimizu S, Tsujimura T, Nakano T. Pemetrexed for epithelioid haemangioendothelioma of the pleura. Respirol Case Rep. 2016;4(6):e00191.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Pinet C, Magnan A, Garbe L, Payan MJ, Vervloet D. Aggressive form of pleural epithelioid haemangioendothelioma: complete response after chemotherapy. Eur Respir J. 1999;14(1):237.PubMedCrossRefGoogle Scholar
  30. 30.
    Merikas E, Grapsa D, Dikoudi E, Gkiozos I, Boura P, Charpidou A, et al. Epithelioid hemangioendothelioma treated with bevacizumab: a case series. Cancer Treat Commun. 2015;4(Supplement C):59–64.CrossRefGoogle Scholar
  31. 31.
    Gaur S, Torabi A, O’Neill TJ. Activity of angiogenesis inhibitors in metastatic epithelioid hemangioendothelioma: a case report. Cancer Biol Med. 2012;9(2):133–6.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Belmont L, Zemoura L, Couderc LJ. Pulmonary epithelioid haemangioendothelioma and bevacizumab. J Thoracic Oncol : Off Publ Int Assoc Study Lung Cancer. 2008;3(5):557–8.CrossRefGoogle Scholar
  33. 33.
    Kim YH, Mishima M, Miyagawa-Hayashino A. Treatment of pulmonary epithelioid hemangioendothelioma with bevacizumab. J Thorac Oncology: Off Publ Int Assoc Study Lung Cancer. 2010;5(7):1107–8.CrossRefGoogle Scholar
  34. 34.
    Mizota A, Shitara K, Fukui T. Bevacizumab chemotherapy for pulmonary epithelioid hemangioendothelioma with severe dyspnea. J Thorac Oncol : Off Publ Int Assoc Study Lung Cancer. 2011;6(3):651–2.CrossRefGoogle Scholar
  35. 35.
    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(4):229–36.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Salech F, Valderrama S, Nervi B, Rodriguez JC, Oksenberg D, Koch A, et al. Thalidomide for the treatment of metastatic hepatic epithelioid hemangioendothelioma: a case report with a long term follow-up. Ann Hepatol. 2011;10(1):99–102.PubMedGoogle Scholar
  37. 37.
    Mascarenhas RC, Sanghvi AN, Friedlander L, Geyer SJ, Beasley HS, Van Thiel DH. Thalidomide inhibits the growth and progression of hepatic epithelioid hemangioendothelioma. Oncology. 2004;67(5–6):471–5.PubMedCrossRefGoogle Scholar
  38. 38.
    Raphael C, Hudson E, Williams L, Lester JF, Savage PM. Successful treatment of metastatic hepatic epithelioid hemangioendothelioma with thalidomide: a case report. J Med Case Rep. 2010;4:413.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Kassam A, Mandel K. Metastatic hepatic epithelioid hemangioendothelioma in a teenage girl. J Pediatr Hematol Oncol. 2008;30(7):550–2.PubMedCrossRefGoogle Scholar
  40. 40.
    Bolke E, Gripp S, Peiper M, Budach W, Schwarz A, Orth K, et al. Multifocal epithelioid hemangioendothelioma: case report of a clinical chamaeleon. Eur J Med Res. 2006;11(11):462–6.PubMedGoogle Scholar
  41. 41.
    Pallotti MC, Nannini M, Agostinelli C, Leoni S, Scioscio VD, Mandrioli A, et al. Long-term durable response to lenalidomide in a patient with hepatic epithelioid hemangioendothelioma. World J Gastroenterol: WJG. 2014;20(22):7049–54.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Zheng Z, Wang H, Jiang H, Chen E, Zhang J, Xie X. Apatinib for the treatment of pulmonary epithelioid hemangioendothelioma: a case report and literature review. Medicine. 2017;96(45):e8507.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Kobayashi N, Shimamura T, Tokuhisa M, Goto A, Ichikawa Y. Sorafenib monotherapy in a patient with Unresectable hepatic epithelioid Hemangioendothelioma. Case Rep Oncol. 2016;9(1):134–7.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    • Semenisty V, Naroditsky I, Keidar Z, Bar-Sela G. Pazopanib for metastatic pulmonary epithelioid hemangioendothelioma-a suitable treatment option: case report and review of anti-angiogenic treatment options. BMC Cancer. 2015;15:402. Although only a case report, this paper provides a review of antiangiogenic agents for the treatment of this diseasePubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Mao X, Liang Z, Chibhabha F, Ou W, Li N, Xu P, et al. Clinico-radiological features and next generation sequencing of pulmonary epithelioid hemangioendothelioma: a case report and review of literature. Thorac Cancer. 2017;8(6):687–92.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Lerut JP, Orlando G, Adam R, Schiavo M, Klempnauer J, Mirza D, et al. The place of liver transplantation in the treatment of hepatic epitheloid hemangioendothelioma: report of the European liver transplant registry. Ann Surg. 2007;246(6):949–57. discussion 57PubMedCrossRefGoogle Scholar
  47. 47.
    Agrawal N, Parajuli S, Zhao P, Satoskar R, Laurin J, Azumi N, et al. Liver transplantation in the management of hepatic epithelioid hemangioendothelioma: a single-center experience and review of the literature. Transplant Proc. 2011;43(7):2647–50.PubMedCrossRefGoogle Scholar
  48. 48.
    Fang C, Zhang W, Zheng S. Liver transplantation for hepatic epithelioidhemangioendothelioma: a casereport and literature review. Int J Clin Exp Med. 2017;10(6):9693–6.Google Scholar
  49. 49.
    Saste A, Cabrera Fernandez DF, Gulati R, Gamalski S. A trimodality approach in the management of metastatic low-grade epithelioid hemangioendothelioma of the bone. BMJ Case Rep 2015;2015.Google Scholar
  50. 50.
    Stacchiotti S, Provenzano S, Dagrada G, Negri T, Brich S, Basso U, et al. Sirolimus in advanced epithelioid hemangioendothelioma: a retrospective case-series analysis from the Italian rare cancer network database. Ann Surg Oncol. 2016;23(9):2735–44.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Hematology/OncologyNorthwestern University, Feinberg School of MedicineChicagoUSA

Personalised recommendations