Surg Today (2006) 36:1024–1027DOI 10.1007/s00595-006-3292-8

Reprint requests to: Y. SugawaraReceived: December 8, 2005 / Accepted: May 16, 2006

Living Donor Liver Transplantation for EpithelioidHemangioendothelioma: Report of a Case

Kiyoshi Hasegawa1, Yasuhiko Sugawara1, Mami Ikeda1, Takeaki Ishizawa1, Kenichi Ohashi2,and Masatoshi Makuuchi1

1 Artificial Organ and Transplantation Division, Department of Surgery, and 2 Department of Pathology, Graduate School of Medicine,University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan

trophic spleen (Fig. 1). No other sign of metastasis wasdetected in the bone, lung, or brain. Needle liver biopsyrevealed that the epithelioid tumor cells were positivefor CD31 and CD34, and had small vacuoles in slightlyeosinophilic cytoplasm. They proliferated diffusely andformed an alveolar and trabecular pattern in the myxoidstroma. We performed living donor liver transplanta-tion with splenectomy, and immunosuppression wasmaintained by tacrolimus and steroids. Microscopic ex-amination of the spleen confirmed that the lesions weremetastatic.

The patient complained of intermittent lumbago andpain in both her legs 3 months after liver transplanta-tion. A bone scintigram showed metastasis in the iliacbone, and computed tomography showed numeroussmall low-density spots in the liver graft, suggesting in-trahepatic metastases. Despite a course of oral tegafur-uracil, her general condition deteriorated and she died 8months after the liver transplantation.

Discussion

Since EH was first described,1 it has become evidentthat its malignant potential is unpredictable with anintermediate clinical course between benign heman-gioma and malignant hemangiosarcoma. Thus, withsuch wide biologic characteristics, it is difficult to evalu-ate the effectiveness of a particular treatment. Previousstudies suggest that extrahepatic metastasis is nota prognostic factor after liver transplantation forEH;2,4,8–12,14 however, it is paradoxical that the presenceof metastasis at transplantation would be associatedwith better post-transplant prognosis for a malignantdisease.

To re-evaluate the clinical effectiveness of liver trans-plantation for EH, we reviewed 13 studies4,6–16 docu-menting long-term results after liver transplantation forEH. Of the 41 patients studied, including our patient

AbstractEpithelioid hemangioendothelioma (EH) of the liver isa rare tumor, generally considered to have low-grademalignancy. Little is known about its clinical behaviorand the therapeutic strategy is not established. We re-port the case of a 36-year-old woman who underwentliving donor liver transplantation for EH with splenicmetastases and died of recurrence 8 months later. Todetermine if transplantation improves the prognosis ofpatients with EH, we must re-evaluate its indications.

Key words Epithelioid hemangioendothelioma · Livertransplantation · Living donor

Introduction

Epithelioid hemangioendothelioma (EH) of the liver isa rare vascular neoplasm, which originates from endot-helial cells.1–3 Although it is generally considered to bea low-grade malignancy,1–5 the clinical progressionand natural history of EH remain unknown.1–4,6 Livertransplantation is thought to be the most effectivetherapeutic choice for EH;2,4,5,7–13 however, its clinicalimplications are under debate.

Case Report

A 36-year-old woman was referred to our departmentfor investigation of general fatigue and itching. She re-ported no history of oral contraceptive use. Computedtomography showed numerous small low-density spotsin the liver and two low-density nodules in a hyper-

1025K. Hasegawa et al.: LT for Epithelioid Hemangioendothelioma

(Table 1), extrahepatic metastasis was found pre- orintraoperatively in 16 (Metastasis group, 39%), and notfound in 25 (No-metastasis group, 61%). The patientsurvival rate of the Metastasis group tended to be betterthan that of the No-metastasis group, although thedifference was not significant (P ± 0.09, Fig. 2). Therecurrence-free survival curves of these two groupsoverlapped.

We suspect that the patients with metastases mighthave survived longer without liver transplantation, al-though this assumption is based on weak evidence, be-

Table 1. Reported cases of liver transplantation for epithelioid hemangioendothelioma

Age Follow-up Time toFirst (years)/ Extrahepatic period Recurrence recurrenceauthorRef. Year Sex metastasis (months) Prognosis site (months)

Scoazec7 1988 ND None 14 ANR — —ND None 16 ANR — —

Marino8 1988 ND Lung, diaphragm, pleura 132 ANR — —ND None 48 ANR — —ND None 16 DR Liver, lung 12ND PHLN, common bile duct 24 AR Mediastinum, lung 18ND EHLN, lung 16 ANR — —ND PHLN 16 ANR — —ND EHLN 15 ANR — —ND None 9 ANR — —ND None 1 ANR — —ND None 3 DR Liver, lung 2

Kelleher4 1989 27/F Omentum, lung 134 ANR — —29/F PHLN 30 ANR — —29/M PHLN 29 ANR — —24/F PHLN 29 ANR — —40/F None 12 ANR — —33/F None 65 AR Mediastinum 5626/F None 16 DR Lung 1230/M PHLN 31 AR Mediastinum 2037/Ma PHLN, rib 27 AR Lung 1754/M Lung 5 AR Femoral bone 3

Van de Stadt13 1989 34/M None 23 DR Local recurrence 20Demetris15 1997 46/F None 41 AR Liver 36Hung9 1998 27/M None 24 AR Mesenterium NDb

Ben-Haim10 1999 40/M None 29 DR Liver NDb

25/Fa Diaphragm, peritoneal 96 AR Liver 4853/M None 30 ANR — —34/M Spleen, EHLN 32 AR ND NDb

61/M None 84 DR Liver, bone NDb

d’Annibale6 2002 26/F None 11 ANR — —Kayler11 2002 21/F None 16 DR Mesenterium 2St Peter16 2003 46/M None 36 ANR — —Simpson14 2003 36/F None 36 ANR — —Lerut12 2004 25/F None 166 DR Breast 156

42/M None 165 ANR — —45/F None 115 ANR — —26/Ma Cervical vertebrae 56 ANR — —26/M None 41 ANR — —24/F None 22 ANR — —

Present case 2005 36/F Spleen 8 DR Liver, bone 6

EH, epithelioid hemagioendothelioma; ND, no data; PHLN, porta hepatis lymph node; EHLN, extrahepatic lymph node; ANR, alive with norecurrence; AR, alive with recurrence; DR, died of recurrencea Extrahepatic metastasis was removed in three patients and not documented in the remaining 13b We excluded four cases from the analysis of recurrence-free survival, because time to recurrence was not documented

cause the patients we reviewed were treated by differ-ent protocols with various follow-up periods in manyinstitutes. As it is impossible to predict the therapeuticeffects of liver transplantation for EH, further sys-tematic investigations and long-term observations arenecessary.

Acknowledgments. This report was supported by a grant fromthe Kanae Foundation for Life and Socio-medical Science (toK.H.), a Grant-in-Aid for Scientific Research from the Minis-try of Education, Culture, Sports, Science and Technology of

1026 K. Hasegawa et al.: LT for Epithelioid Hemangioendothelioma

Japan (to Y.S.), and Grants-in-aid for Research on HIV/AIDS (to Y.S.). This report was prepared as a part of amulticenter pilot clinical study to compare the safety andefficacy of a steroid-free immunosuppression protocol withmonoclonal anti-IL2R antibody in HCV positive living donorliver transplantation (to M.M.) and Research on Measures forIntractable Diseases (to M.M.) from the Ministry of Health,Labour, and Welfare of Japan.

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Fig. 1. Preoperative enhanced computed tomography showedsmall low-density spots scattered in the liver, and a low-density nodule in the spleen (arrow)

Fig. 2. Patient (A) and recurrence-free (B) survival curvesafter liver transplantation for epithelioid hemangioendothe-lioma in patients with (thick line) and those without (thin line)extrahepatic metastasis. We excluded one patient from theMetastasis group and three from the No-metastasis groupfrom the analysis on recurrence-free survival, because of thelack of data on recurrence

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