Our experience of liver Epithelioid Hemangioendothelioma: from a misdiagnosis to liver transplantation with long term follow-up

Antonio Giuliani 1 , Bruno Amato 2 , Giuseppina Marino Marsilia 3 , Domenico Tafuri 4 , Antonio Ceriello 1 , Walter Santaniello 1 , Loredana Sodano 1 , and Aldo Rocca 1
  • 1 Unit of Hepatobiliary Surgery and Liver Transplant Center, Department of Gastroenterology and Transplantation,”A. Cardarelli” Hospital, Naples, Italy
  • 2 Department of Clinical Medicine and Surgery, University of Naples Federico II, Italy
  • 3 Department of Pathology, A. Cardarelli Hospital, Naples, Italy
  • 4 Department of Sport Sciences and Wellness, University of Naples “Parthenope”, Naples, Italy

Abstract

Malignant Hepatic Epithelioid hemangioendothelioma (HEHE) is an uncommon vascular tumor of intermediate malignant potential. HEHE is a rare tumor and it is difficult to diagnose for surgeons, hepatologists, radiologists and pathologists. So, misdiagnosis with a delay of the treatment is not uncommon. We describe a case of a young woman with a diagnosis of HEHE made 6 years after the first evidence of liver mass with a very long term follow-up after surgical treatment. She had two diagnoses of Hepatocellurar carcinoma (HCC) and a diagnosis of Cholangiocarcinoma after three different fine needle biopsies. After clinical observation, a new laparoscopic core biopsy was performed. In a first time approach, considering clinical and radiological patterns, a diagnosis of Budd-Chiari Syndrome was finally made. For that the patient underwent an orthotopicliver transplantation (OLTx). The surgical sample histological analysis allowed a definitive diagnosis of HEHE. At last, at follow up 7 years after three OLTx the patient is still alive and in good health with no evidence of recurrence.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • [1] Makhlouf HR, Ishak KG and Goodman ZD.Epithelioidhemang ioendothelioma of the liver: a clinicopathologic study of 137 cases. Cancer 1999; 85: 562582

  • [2] Richardson WS, Stefanidis D, Chang L, Earle DB and Fanelli RD. The role of diagnostic laparoscopy for chronic abdominal conditions: an evidencebased review. SurgEndosc 2009; 23: 20732077

  • [3] Mehrabi A, Kashfi A, Fonouni H, et al. Primary malignant hepatic epithelioidhemangioendothelioma: a comprehensive review of the literature with emphasis on the surgical therapy. Cancer 2009;107: 21082121, 2006

  • [4] Rocca A, Calise F, Marino G, Montagnani S, Cinelli M, Amato B et al.:Primary giant hepatic neuroendocrine carcinoma: A case report.Int J Surg. 2014;12Suppl 1:S218-21

  • [5] Ishak KG, Sesterhenn IA, Goodman ZD, Rabin L, Stromeyer FW. Epithelioidhemangioendothelioma of the liver: a clinicopathologic and follow-up study of 32 cases. Hum Pathol 1984; 15: 839-852

  • [6] Scialpi M, Palumbo B, Pierotti L, Gravante S, Piunno A, Rebonato A et al. Detection and characterization of focalliverlesions by split-bolusmultidetector-row CT: diagnosticaccuracy and radiation dose in oncologicpatients. Anticancer Res. 2014 Aug;34(8):4335-4344

  • [7] Liu L, Kakiuchi-Kiyota S, Arnold LL, Johansson SL, Wert D, Cohen SM. Pathogenesis of human hemangiosarcomas and hemangiomas. Hum Pathol. 2013 Oct;44(10):2302-2311

  • [8] Dragoni S, Laforenza U, Bonetti E, Lodola F, Bottino C, Guerra G et al.: Canonical Transient Receptor Potential 3 channel triggers VEGF-induced intracellular ca2+ oscillations in endothelial progenitor cells isolated from umbilical cord blood. Stem Cells and Development 2013 Oct 1;22(19):2561-2580

  • [9] Dragoni S, Laforenza U, Bonetti E, Lodola F, Bottino C, Berra-Romani R et al.: Vascular endothelial growth factor stimulates endothelial colony forming cells proliferation and tubulogenesis by inducing oscillations in intracellular Ca2+ concentration. Stem Cells. 2011 Nov;29(11):1898-1907

  • [10] Sanchez-Hernandez Y, Laforenza U, Bonetti E, Fontana J, Dragoni S, Russo Met al.: Store operated Ca2+ entry is expressed in human endothelial progenitor cells. Stem Cells and Development 2010 Dec;19(12):1967-1981

  • [11] Berra-Romani R, Raqeeb A, Torres-Jácome J, Guzman-Silva A, Guerra G, Tanzi F et al.:The mechanism of injury-induced intracellular calcium concentration oscillations in the endothelium of excised rat aorta.J Vasc Res. 2012;49(1):65-76

  • [12] Potenza DM, Guerra G, Avanzato D, Poletto V, Pareek S, Guido D et al.:Hydrogen sulphide triggers VEGF-induced intracellular Ca2+ signals in human endothelial cells but not in their immature progenitors. Cell Calcium. 2014 Sep;56(3):225-234

  • [13] Dragoni S, Guerra G, PlaAf, Bertoni G, Rappa A, Poletto V et al.:A Functional Transient Receptor Potential Vanilloid 4 (Trpv4) Channel Is Epxressed In Human Endothelial Progenitor Cells.J Cell Physiol 2015 Jan;230(1):95-104

  • [14] Moccia F, Dragoni S, Lodola F, Bonetti E, Bottino C, Guerra G et al.: Store-dependent Ca2+ entry in endothelial progenitor cells as a perspective tool to enhance cell-based therapy and adverse tumourvascularisation. Curr Med Chem 2012 Dec 1;19(34):5802-5818.

  • [15] Moccia F, Lodola F, Dragoni S, Bonetti E, Bottino C, Guerra G et al.: Ca2+ signalling in endothelial progenitor cells: a novel means to improve cell-based therapy and impair tumourvascularisation. CurrVascPharmacol. 2014 Jan;12(1):87-105

  • [16] Lodola F, Laforenza U, Bonetti E, Lim D, Dragoni S, Bottino C, Ong HL et al.: Store-operated ca(2+) entry is remodelled and controls in vitro angiogenesis in endothelial progenitor cells isolated from tumoral patients. PLoS One 2012 7(9):e42541

  • [17] Berra-Romani R, Avelino-Cruz JE, Raqeeb A, Della Corte A, Cinelli M, Montagnani S, Guerra G, Moccia F, Tanzi F. Ca2+-dependent nitric oxide release in the injured endothelium of excised rat aorta: a promising mechanism applying in vascular prosthetic devices in aging patients. BMC Surg 2013 Oct 8;13(Suppl 2):S40

  • [18] Moccia F, Dragoni S, Cinelli M, Montagnani S, Amato B, Rosti V et al.: How to utilize Ca2+ signals to rejuvenate the repairative phenotype of senescent endothelial progenitor cells in elderly patients affected by cardiovascular diseases: a useful therapeutic support of surgical approach? BMC Surg 2013 Oct 8;13(Suppl 2):S46

  • [19] Dragoni S, Laforenza U, Bonetti E, Reforgiato M, Poletto V, Lodola F et al.: Enhanced Expression of Stim, Orai, and TRPC Transcripts and Proteins in Endothelial Progenitor Cells Isolated from Patients with Primary Myelofibrosis. PLoS One 2014 Mar 6;9(3):e91099

  • [20] Dragoni S, Turin I, Laforenza U, Potenza DM, Bottino C, Glasnov TN, et al.:Store-operated ca(2+) entry does not control proliferation in primary cultures of human metastatic renal cellular carcinoma. Biomed Res Int. 2014;2014:739494

  • [21] Moccia F, Guerra G. Ca2+ Signalling in Endothelial Progenitor Cells: Friend or Foe? J Cell Physiol. J Cell Physiol. 2016 Feb;231(2):314-27. doi: 10.1002/jcp.25126

  • [22] Moccia F, Zuccolo E, Poletto V, Cinelli M, Bonetti E, Guerra G et al.:. Endothelial progenitor cells support tumour growth and metastatisation: implications for the resistance to anti-angiogenic therapy. Tumour Biol. 2015 Aug 2.

  • [Epub ahead of print]

  • [23] Dragoni S, Reforgiato M, Zuccolo E, Poletto V, Lodola F, Ruffinatti FA et al.:Dysregulation of VEGF-induced pro-angiogenic Ca2+ oscillations in primary myelofibrosisderived endothelial colony forming cells. ExpHematol. 2015 Sep 30.pii: S0301-472X(15)00663-3

  • [24] Remiszewski P, Szczerba E, Kalinowski P, Gierej B, Dudek K, Grodzicki M et al.:Epithelioidhemangioendothelioma of the liver as a rare indication for liver transplantation World J Gastroenterol 2014 August 28; 20(32): 11333-11339

  • [25] Hayashi Y, Inagaki K, Hirota S, Yoshikawa T, Ikawa H. Epithelioid hemangioendothelioma with marked liver deformity and secondary Budd-Chiari Syndrome: pathological and radiological correlation. Pathol Int 1999; 49: 547-552

  • [26] Clements D, Hubscher S, West R, Elias E, McMaster P. Epithelioid haemangioendothelioma. A case report.J Hepatol 1986; 2: 441-449

  • [27] Otrock ZK, Al-Kutoubi A, Kattar MM, Zaatari G, Soweid A. Spontaneous complete regression of hepatic epithelioidhaemangioendothelioma. Lancet Oncol2006; 7: 439-441

  • [28] Neofytou K, Chrysochos A, Charalambous N, Dietis M, Petridis C, Andreou C et al. Hepatic Epithelioid Hemangioendothelioma and the Danger of Misdiagnosis: Report of a Case. Case Rep OncolMed. 2013: 243939

  • [29] Demetris AJ, Minervini M, Raikow RB, and Lee RG. Hepatic epithelioid hemangioendothelioma: Biological questions based on pattern of recurrence in an allograft and tumor immunophenotype, American Journal of Surgical Pathology, 1997 vol. 21, no. 3, pp. 263-270

  • [30] Langrehr JM, Petersen I, Pfitzmann R, and Lopez-Hanninen E. Malign epithelioid hemangioendothelioma of the liver. Results of surgical treatment strategies” Chirurg, 2005;76,(12):161-1167.

  • [31] Miller WJ, Dodd GD, Federle MP, and Baron RL. Epithelioid hemangioendothelioma of the liver: imaging findings with pathologic correlation,” American Journal of Roentgenology 1992; 159(1):53-57

  • [32] Giuliani A, Migliaccio C, Ceriello A, Aragiusto G, La Manna G, Calise F.Laparoscopic vs. open surgery for treating benign liver lesions: assessing quality of life in the first year after surgery. UpdatesSurg. 2014 Jun;66(2):127-133

  • [33] Deyrup AT, Tighiouart M, Montag AG and Weiss SW.Epithelioid hemangioendothelioma of soft tissue: a proposal for risk stratification based on 49 cases, The American Journal of Surgical Pathology 2008; 32:924-927

  • [34] Rodriguez JA, Becker NS, O’Mahony CA, Goss JA, Aloia TA. Long-term outcomes following liver transplantation for hepatic hemangioendothelioma: the UNOS experience from 1987 to 2005. J GastrointestSurg 2008; 12:110-116

  • [35] Giuliante F, Ardito F, Ranucci G, Giovannini I, Nuzzo G. Giant focal nodular hyperplasia determining Budd-Chiari Syndrome: an operative challengerequiring 210 min of liver ischemia UpdatesSurg. 2011 Dec;63(4):307-311

  • [36] Lerut JP, Orlando G, Adam R, Schiavo M, Klempnauer J, Mirza D et al. The place of liver transplantation in the treatment of hepatic epithelioid hemangioendothelioma: report of the European liver transplant registry. Ann Surg 2007; 246:949-957

OPEN ACCESS

Journal + Issues

Search